APP transgenesis: Approaches toward the development of animal models for Alzheimer disease neuropathology

Neurobiology of Aging

Volumn 17, Issue 2, 1996, Pages 153-171

  Greenberg, Barry D ^a   Savage, Mary J ^a   Howland, David S ^a   Ali, Shujath M ^b   Siedlak, Sandi L ^c   Perry, George ^c   Siman, Robert ^a   Scott, Richard W ^a  

^a CEPHALON INC   (United States)

^b GLAXOSMITHKLINE   (United Kingdom)

^c CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID PRECURSOR PROTEIN;

ALZHEIMER DISEASE; ANIMAL MODEL; HUMAN; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; REVIEW; TRANSGENIC ANIMAL;

EID: 0029949755     PISSN: 01974580     EISSN: None     Source Type: Journal    
DOI: 10.1016/0197-4580(96)00001-2     Document Type: Article

References (323)

1. 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease. Cell 52:487-501;1988.
2. Ali, S. M.; Siedlak, S. L.; Gonzalez-DeWhitt, P. A.; Altman, R. A.; Glendening, J. M.; Lowery, D. E.; Savage, M. J.; Polites, H. G.; Perry, G.; Greenberg, B. D. Artifactual strain-specific signs of incipient brain amyloidosis in APP transgenic mice. Neurobiol. Aging 17:223-234; 1996.
3. Allen, N. D.; Norris, M. L.; Surani, M. A. Epigenetic control of transgene expression and imprinting by genotype-specific modifiers. Cell 61:853-861; 1990.
4. Anderson, J. P.; Refolo, L. M.; Wallace, W.; Mehta, P.; Krishnamurthi, M.; Gotlib, J.; Bierer, L.; Haroutunian, V.; Perl, D.; Robakis, N. K. Differential brain expression of the Alzheimer's amyloid precursor protein. EMBO J. 8:3627-3632; 1989.
5. Anderson, J. P.; Esche, F. S.; Keim, P. S.; Sambamurti, K.; Lieberburg, I.; Robakis, N. K. Exact cleavage site of Alzheimer amyloid precursor in neuronal PC-12 cells. Neurosci. Lett. 128:126-128; 1991.
6. Arai, H.; Lee, V. M.-Y.; Greenberg, B. D.; Lowery, D. E.; Sharma, S. K.; Schmidt, M. L.; Trojanowski, J. Q. Defined neurofilament, τ and β-amyloid precursor protein epitopes distinguish Alzheimer from non-Alzheimer senile plaques. Proc. Natl. Acad. Sci. USA 87:2249-2253; 1990.
7. Araki, S.; Yi, S.; Murakami, T.; Watanabe, S.; Ikegawa, S.; Takahashi, K.; Yamarnura, K. Systemic amyloidosis in transgenic mice carrying the human mutant transthyretin (Met30) gene: Pathological and immunohistochemical similarity to human familial amyloidotic polyneuropathy. Mol. Neurobiol. 8:15-23; 1994.
8. Bahmanyar, S.; Higgins, G. A.; Goldgaber, D.; Lewis, D. A.; Morrison, J. H.; Wilson, M. C.; Shankar, S. K.; Gajdusek, D. C. Localization of amyloid β protein messenger RNA in brains from patients with Alzheimer's disease. Science 237:77-80; 1987.
9. Banati, R. B.; Gehrmann, J.; Czech, C.; Mönning, U.; Jones, L. L.; König, G.; Beyreuther, K.; Kreutzberg, G. W. Early and rapid de novo synthesis of Alzheimer βA4-amyloid precursor protein (APP) in activated microglia. Glia 9:199-210; 1993.
10. Barrow, C. J.; Zagorski, M. G. Solution structures of β peptide and its constituent fragments: Relation to amyloid deposits. Science 253: 179-182; 1991.
11. Barrow, C. J.; Yasuda, A.; Kenny, P. T. M.; Zagorski, M. G. Solution conformations and aggregational properties of synthetic amyloid β-peptides of Alzheimer's disease. J. Mol. Biol. 225:1075-1093; 1992.
12. Bauer, J.; König, G.; Strauss, S.; Jonas, U.; Ganter, U.; Weidemann, A. Mönning, U.; Masters, C. L.; Volk, B.; Berger, M.; Beyreuther, K. In vitro matured human macrophages express Alzheimer's βA4-amyloid precursor protein indicating synthesis in microglial cells. FEBS Lett. 282:335-340; 1991.
13. Beck, I.; Ramirez, S.; Weinmann, R.; Caro, J. Enhancer element at the 3′-flanking region controls transcriptional response to hypoxia in the human erythropoietin gene. J. Biol. Chem. 266:15563-15566; 1991.
14. Benowitz, L. I.; Rodriguez, W.; Paskevich, P.; Mufson, E. J.; Schenk, D.; Neve, R. L. The amyloid precursor protein is concentrated in neuronal lysosomes in normal and Alzheimer's disease subjects. Exp. Neurol. 106:237-250; 1989.
15. Blobel, G. A.; Hanafusa, H. The v-src inducible gene 9E3/pCEF4 is regulated by both its promoter upstream sequence and its 3′ untranslated region. Proc. Natl. Acad. Sci. USA 88:1162-1166; 1991.
16. Aγ globin gene. EMBO J. 6:2997-3004; 1987.
17. Bondareff, W.; Wischik, C. M.; Novak, M.; Amos, W. B.; Klug, A.; Roth, M. Molecular analysis of neurofibrillary degeneration in Alzheimer's disease: An immunohistochemical study. Am. J. Pathol. 137:711-723; 1990.
18. Bons, N.; Mestre, N.; Petter, A. Senile plaques and neurofibrillary changes in the brain of an aged lemurian primate, Microcebus murinus. Neurobiol. Aging 13:99-105; 1991.
19. Bons, N.; Mestre, N.; Ritchie, K.; Petter, A.; Podlisny, M.; Selkoe, D. J. Identification of amyloid beta protein in the brain of the small, short-lived lemurian primate Microcebus murinus. Neurobiol. Aging 15:215-220; 1994.
20. Bradley, A.; Hasty, P.; Davis, A.; Ramirez-Solis, R. Modifying the mouse: Design and desire. Bio/Technology 10:534-539; 1992.
21. Bramblett, G. T.; Trojanowski, J. Q.; Lee, V. M.-Y. Regions with abundant neurofibrillary pathology in human brain exhibit a selective reduction in levels of binding-competent T and accumulation of abnormal T isoforms (A68 proteins). Lab. Invest. 66:212-222; 1992.
22. Brinster, R. L.; Chen, H. Y.; Trumbauer, M. E.; Yagle, M. K.; Palmiter, R. D. Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs. Proc. Natl. Acad. Sci. USA 82:4438-4442; 1985.
23. Brinster, R. L.; Allen, J. M.; Behringer, R. R.; Gelinas, R. E.; Palmiter, R. D. Introns increase transcriptional efficiency in transgenic mice. Proc. Natl. Acad. Sci. USA 85:836-840; 1988.
24. Burdick, D.; Soreghan, B.; Kwon, M.; Kosmoski, J.; Knauer, M.; Heenschen, A.; Yates, J.; Cotman, C.; Glabe, C. Assembly and aggregation properties of synthetic Alzheimer's A4/β amyloid peptide analogs. J. Biol. Chem. 267:546-564; 1992.
25. Busciglio, J.; Gabuzda, D. H.; Matsudaira, P.; Yankner, B. A. Generation of β-amyloid in the secretory pathway in neuronal and nonneuronal cells. Proc. Natl. Acad. Sci. USA 90:2092-2096; 1993.
26. Bush, A. I.; Martins, R. N.; Rumble, B.; Moir, R.; Fuller, S.; Milward, E.; Currie, J.; Ames, D.; Weidemann, A.; Fischer, P.; Multhaup, G.; Beyreuther, K.; Masters, C. L. The amyloid precursor protein of Alzheimer's disease is released by human platelets. J. Biol. Chem. 265:15977-15983; 1990.
27. Butler, A.; Whitehead, A. S. Resistance to secondary amyloidosis in A/J mice is not significantly associated with allelic variants linked to the serum amyloid A gene cluster. Scand. J. Immunol. 40:355-358; 1994.
28. Buxbaum, J. D.; Christensen, J. L.; Ruefli, A. A.; Greengard, P.; Loring, J. F. Expression of APP in brains of transgenic mice containing the entire human APP gene. Biochem. Biophys. Res. Commun. 197: 639-645; 1993.
29. Cai, X. D.; Golde, T. E.; Younkin, S. G. Release of excess amyloid β protein from a mutant amyloid β protein precursor. Science 259:514-516; 1993.
30. Capecchi, M. R. Altering the genome by homologous recombination. Science 244:1288-1292; 1989.
31. Capecchi, M. R. The new mouse genetics: Altering the genome by gene targeting. Trends Genet. 5:70-76; 1989.
32. Caporaso, G. L.; Gandy, S. E.; Buxbaum, J. D.; Ramabhadran, T. V.; Greengard, P. Protein phosphorylation regulates secretion of Alzheimer β/A4 amyloid precursor protein. Proc. Natl. Acad. Sci. USA 89:3055-3059; 1992.
33. Card, J. P.; Meade, R. M.; Davis, L. G. Immunocytochemical localization of the precursor for β-amyloid in the rat CNS. Neuron 1:835-846; 1988.
34. Chartier-Harlin, M. C.; Crawford, F.; Houlden, H.; Warren, A.; Hughes, D.; Fidani, L.; Goate, A.; Rossor, M.; Roques, P.; Hardy, J.; Mullan, M. Early onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene. Nature 353:844-846; 1991.
35. Cheung, T. T.; Ghiso, J.; Shoji, M.; Cai, X.-D.; Golde, T.; Gandy, S.; Frangione, B.; Younkin, S. G. Characterization by radiosequencing of the carboxyl-terminal derivatives produced from normal and mutant amyloid protein precursors. Amyloid: Int. J. Exp. Clin. Invest. 1:30-38; 1994.
36. Choi, T.; Huang, M.; Gorman, C.; Jaenisch, R. A generic intron increases gene expression in transgenic mice. Mol. Cell. Biol. 11:3070-3074; 1991.
37. Citron, M.; Oltersdorf, T.; Haass, C.; McConlogue, L.; Hung, A. Y.; Seubert, P.; Vigo-Pelfrey, C.; Lieberburg, I.; Selkoe, D. J. Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production. Nature 360:672-674; 1992.
38. Citron, M.; Vigo-Pelfrey, C.; Teplow, D. B.; Miller, C.; Schenk, D.; Johnston, J.; Winblad, B.; Venizelos, N.; Lannfelt, L.; Selkoe, D. J. Excessive production of amyloid β-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation. Proc. Natl. Acad. Sci. USA 91: 11993-11997; 1994.
39. Clemens, J. A.; Stephenson, D. T. Implants containing β-amyloid protein are not neurotoxic to young and old rat brain. Neurobiol. Aging 13:581-586; 1992.
40. 21 to Gly on the aggregation of a synthetic fragment of the Alzheimer's amyloid β/A4 peptide. Neurosci. Lett. 161:17-20; 1993.
41. Cohen, M. L.; Golde, T. E.; Usiak, M. F.; Younkin, L. H.; Younkin, S. G. In situ hybridization of nucleus basalis neurons shows increased β-amyloid mRNA in Alzheimer's disease. Proc. Natl. Acad. Sci. USA 85:1227-1231; 1988.
42. Corder, E. H.; Saunders, A. M.; Strittmatter, W. J.; Schmechel, D. E.; Gaskell, P. C.; Small, G. W.; Roses, A. D.; Haines, J. L.; Pericak-Vance, M. A. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science 261:921-923; 1993.
43. Corder, E. H.; Saunders, A. M.; Risch, N. J.; Strittmatter, W. J.; Schmechel, D. E.; Gaskell, P. C.; Rimmler, J. B.; Locke, P. A.; Conneally, P. M.; Schmader, K. E.; Small, G. W.; Roses, A. D.; Haines. J. L.; Pericak-Vance, M. A. Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat. Genet. 7:180-184; 1994.
44. Côté, F.; Collard, J.-F.; Julien, J.-P. Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: A mouse model of amyotrophic lateral sclerosis. Cell 73:35-46; 1993.
45. Cras, P.; Kawai, M.; Siedlak, S.; Mulvihill, P.; Gambetti, P.; Lowery, D.; Gonzalez-DeWhitt, P.; Greenberg, B.; Perry, G. Neuronal and microglial involvement in β-amyloid protein deposition in Alzheimer's Disease. Am. J. Pathol. 137:241-246; 1990.
46. Cras, P.; Kawai, M.; Lowery, D.; Gonzalez-DeWhitt, P.; Greenberg, B.; Perry, G. Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein. Proc. Natl. Acad. Sci. USA 88:7552-7556; 1991.
47. Crystal, H.; Dickson, D.; Fuld, P.; Masur, D.; Scott, R.; Mehler, M.; Masdeu, J.; Kawas, C.; Aronson, M.; Wolfson, L. Clinico-pathologic studies in dementia: Nondemented subjects with pathologically confirmed Alzheimer's disease. Neurology 38:1682-1687; 1988.
48. Cummings, B. J.; Su, J. H.; Geddes, J. W.; Van Nostrand, W. E.; Wagner, S. L.; Cunningham, D. D.; Cotman, C. W. Aggregation of the amyloid precursor protein within degenerating neurons and dystrophic neurites in Alzheimer's disease. Neuroscience 48:763-777; 1992.
49. Cummings, B. J.; Su, J. H.; Cotman, C. W.; White, R.; Russell, M. J. β-Amyloid accumulation in aged canine brain: A model of early plaque formation in Alzheimer's disease. Neurobiol. Aging 14:547-560; 1993.
50. de Beer, M. C.; de Beer, F. C.; Beach, C. M.; Gonnerman, W. A.; Carreras, I.; Sipe, J. D. Syrian and Armenian hamsters differ in serum amyloid A gene expression. Identification of novel Syrian hamster serum amyloid A subtypes. J. Immunol. 150:5361-5370; 1993.
51. DeKosky, S. T.; Scheff, S. W. Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity. Ann. Neurol. 27:457-464; 1990.
52. deSauvage, F.; Octave, J. N. A novel mRNA of the A4 amyloid precursor gene coding for a possibly secreted protein. Science 245: 651-653; 1989.
53. Dickson, D. W.; Farlo, J.; Davies, P.; Crystal, H.; Fuld, P.; Yen, S. H. C. Alzheimer's Disease: A double-labeling immunohistochemical study of senile plaques. Am. J. Pathol. 132:86-101; 1988.
54. Dovey, H. F.; Suomensaari-Chrysler, S.; Lieberburg, I.; Sinha, S.; Keim, P. Cells with a familial Alzheimer's disease mutation produce authentic β-peptide. Neuroreport 4:1039-1042; 1993.
55. Dyrks, T.; Dyrks, E.; Masters, C. L.; Beyreuther, K. Amyloidogenicity of rodent and human βA4 sequences. FEBS Lett. 324:231-236; 1993.
56. Ellis, W. G.; McCullogh, J. R.; Corley, C. L. Presenile dementia in Down's syndrome - Ultrastructural identity with Alzheimer's disease. Neurology 24:101-106; 1974.
57. Emre, M.; Geula, C.; Ransil, B. J.; Mesulam, M.-M. The acute neurotoxicity and effects upon cholinergic axons of intracerebrally injected β-amyloid in the rat brain. Neurobiol. Aging 13:553-559; 1992.
58. Engler, P.; Haasch, D.; Pinkert, C. A.; Doglio, L.; Glymour, M.; Brinster, R.; Storb, U. A strain-specific modifier on mouse chromosome 4 controls the methylation of independent transgene loci. Cell 65:939-947; 1991.
59. Esch, F. S.; Keim, P. S.; Beattie, E. C.; Blacher, R. W.; Culwell, A. R.; Oltersdorf, T.; McClure, D.; Ward, P. J. Cleavage of amyloid β peptide during constitutive processing of its precursor. Science 248:1122-1124; 1990.
60. Estus, S.; Golde, T. E.; Kunishita, T.; Blades, D.; Lowery, D.; Eisen, M.; Usiak, M.; Qu, X.; Tabira, T.; Greenberg, B. D.; Younkin, S. G. Potentially amyloidogenic, carboxyl-terminal derivatives of the amyloid protein precursor. Science 255:726-728; 1992.
61. Fabian, H.; Szendrei, G. I.; Manisch, H. H.; Ötvös, L. Comparative analysis of human and Dutch-type Alzheimer β-amyloid peptides by infrared spectroscopy and circular dichroism. Biochem. Biophys. Res. Commun. 191:232-239; 1993.
62. Fabian, H.; Szendrei, G. I.; Mantsch, H. H.; Greenberg, B. D.; Ötvös, L. Synthetic posttranslationally modified human Aβ peptide exhibits a markedly increased tendency to form β-pleated sheets in vitro. Eur. J. Biochem. 221:959-964; 1994.
63. Frautschy, S. A.; Baird, A.; Cole, G. M. Effects of injected Alzheimer β-amyloid cores in rat brain. Proc. Natl. Acad. Sci. USA 88:8362-8366; 1991.
64. Frautschy, S. A.; Cole, G. M.; Baird, A. Phagocytosis and deposition of vascular β-amyloid in rat brains injected with Alzheimer β-amyloid. Am. J. Pathol. 140:1389-1399; 1992.
65. Fukuchi, K.; Kamino, K.; Deeb, S. S.; Smith, A. C.; Dang, T.; Martin, G. M. Overexpression of amyloid precursor protein alters its normal processing and is associated with neurotoxicity. Biochem. Biophys. Res. Commun. 182:165-173; 1992.
66. Fukuchi, K.; Kamino, K.; Deeb, S. S.; Furlong, C. E.; Sundstrom, J. A.; Smith, A. C.; Martin, G. M. Expression of a carboxy-terminal region of the β-amyloid precursor protein in a heterogeneous culture of neuroblastoma cells: Evidence for altered processing and selective neurotoxicity. Mol. Brain Res. 16:37-46; 1992.
67. Fukuchi, K. I.; Ogburn, C. E.; Smith, A. C.; Kunkel, D. D.; Furlong, C. E.; Deeb, S. S.; Nochlin, D.; Sumi, S. M.; Martin, G. M. Transgenic animal models for Alzheimer's disease. Ann. NY Acad. Sci. 695:217-223; 1993.
68. Games, D.; Khan, K. M.; Soriano, F. G.; Keim, P. S.; Davis, D. L.; Bryant, K.; Lieberburg, I. Lack of Alzheimer pathology after β-amyloid protein injections in rat brain. Neurobiol. Aging 13:569-576; 1992.
69. Games, D.; Adams, D.; Alessandrini, R.; Barbour, R.; Berthelette, P.; Blackwell, C.; Carr, T.; Clemens, J.; Donaldson, T.; Gillespie, F.; Guido, T.; Hagopian, S.; Johnson-Wood, K.; Khan, K.; Lee, M.; Liebowitz, P.; Lieberburg, I.; Little, S.; Masliah, E.; McConlogue, L.; Montoya-Zavala, M.; Mucke, L.; Paganini, L.; Penniman, E.; Power, M.; Schenk, D.; Seubert, P.; Snyder, B.; Soriano, F.; Tan, H.; Vitale, J.; Wadsworth, S.; Wolozin, B.; Zhao, J. Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 373:523-527; 1995.
70. Ghiso, J.; Tagliavini, F.; Timmers, W. F.; Frangione, B. Alzheimer's disease amyloid precursor protein is present in senile plaques and cerebrospinal fluid: Immunohistochemical and biochemical characterization. Biochem. Biophys. Res. Commun. 163:430-437; 1989.
71. Giaccone, G.; Tagliavini, F.; Linoli, G.; Bouras, C.; Frigerior, L.; Frangione, B.; Bugiani, O. Down's patients: Extracellular preamyloid deposits precede neuritic degeneration and senile plaques. Neurosci. Lett. 97:232-238; 1989.
72. Giaccone, G.; Verga, L.; Finazzi, M.; Pollo, B.; Tagliavini, F.; Frangione, B.; Bugiani, O. Cerebral preamyloid deposits and congophilic angiopathy in aged dogs. Neurosci. Lett. 114:178-183; 1990.
73. Gillespie, S. L.; Golde, T. E.; Younkin, S. G. Secretory processing of the Alzheimer amyloid β/A4 protein precursor is increased by protein phosphorylation. Biochem. Biophys. Res. Commun. 187:1285-1290; 1992.
74. Goate, A. M.; Haynes, A. R.; Owen, M. J.; Farrall, M.; James, L. A.; Lai, L. Y. C.; Mullan, M. J.; Roques, P.; Rossor, M. N.; Williamson, R.; Hardy, J. A. Predisposing locus for Alzheimer's disease on chromosome 21. Lancet i:352-355; 1989.
75. Goate, A.; Chartier-Harlin, M. C.; Mullan, M.; Brown, J.; Crawford, F.; Fidani, L.; Giuffra, L.; Haynes, A.; Irving, N.; James, L.; Mant, R.; Newton, P.; Rooke, K.; Roques, P.; Talbot, C.; Pericak-Vance, M.; Roses, A.; Williamson, R.; Rossor, M.; Owen, M.; Hardy, J. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349:704-706; 1991.
76. Goedert, M. Neuronal localization of amyloid beta protein precursor mRNA in normal human brain and in Alzheimer's disease. EMBO J. 6:3627-3632; 1987.
77. Goedert, M.; Spillantini, M. G.; Cairns, N. J.; Crowther, R. A. Tau proteins of Alzheimer paired helical filaments: Abnormal phosphorylation of all six brain isoforms. Neuron 8:159-168; 1992.
78. Golde, T. E.; Estus, S.; Usiak, M.; Younkin, L. H.; Younkin, S. G. Expression of β amyloid protein mRNAs: Recognition of a novel alternatively spliced form and quantitation in Alzheimer's disease using PCR. Neuron 4:253-267; 1990.
79. Golde, T. E.; Estus, S.; Younkin, L. H.; Selkoe, D. J.; Younkin, S. G. Processing of the amyloid protein precursor to potentially amyloidogenic derivatives. Science 255:728-730; 1992.
80. Goldgaber, D.; Lerman, M. I.; McBride, O. W.; Saffioti, U.; Gajdusek, D. C. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science 250: 877-880; 1987.
81. 1-antichymotrypsin are in the lesions of Alzheimer's disease. Neuroreport 3:201-203; 1992.
82. Gonatas, N. K.; Anderson, W. V.; Evangelista, I. The contribution of altered synapses in the senile plaque: An electron microscopic study in Alzheimer's disease. J. Neuropathol. Exp. Neurol. 26:25-39; 1987.
83. Greenberg, B. D.; Kezdy, F. J.; Kisilevsky, R. Amyloidogenesis as a therapeutic target in Alzheimer's disease. Annu. Rep. Med. Chem. 26:229-238; 1991.
84. Greenberg, B. D.; Ali, S. M.; Howland, D.; Gonzalez-DeWhitt, P. A.; Altman, R. A.; Siedlak, S.; Cras, P.; Scott, R.; Perry, G. Transgenic mouse studies of Alzheimer amyloid precursor. In: Kisilevsky, R.; Benson, E. D.; Frangione, B.; Gauldie, J.; Muckle, T. J.; Young, I. D., eds. Amyloid and Amyloidosis 1993. New York: Parthenon Publishing; 1994:328-331.
85. Greenberg, B. D. The COOH-terminus of the Alzheimer amyloid Aβ peptide: Differences in length influence the process of amyloid deposition in Alzheimer brain, and tell us something about relationships among parenchymal and vessel-associated amyloid deposits. Amyloid: Int. J. Exp. Clin. Invest. 2:195-203; 1995.
86. Gurney, M. E.; Pu, H.; Chiu, A. Y.; Dal Canto, M. C.; Polchow, C. Y.; Alexander, D. D.; Caliendo, J.; Hentati, A.; Kwon, Y. W.; Deng, H.-X.; Chen, W.; Zhai, P.; Sufit, R. L.; Siddique, T. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264:1772-1775; 1994.
87. Haass, C.; Hung, A. Y.; Selkoe, D. J. Processing of β-amyloid precursor protein in microglia and astrocytes favors an internal localization over constitutive secretion. J. Neurosci. 11:3783-3793; 1991.
88. Haass, C.; Schlossmacher, M. G.; Hung, A. Y.; Vigo-Pelfrey, C.; Mellon, A.; Ostaszewski, B. L.; Lieberburg, I.; Koo, E. H.; Schenk, D.; Teplow, D. B.; Selkoe, D. J. Amyloid β-peptide is produced by cultured cells during normal metabolism. Nature 359:322-325; 1992.
89. Haass, C.; Selkoe, D. J. Cellular processing of β-amyloid precursor protein and the genesis of amyloid β-peptide. Cell 75:1039-1042; 1993.
90. Haass, C.; Hung, A. Y.; Schlossmacher, M. G.; Teplow, D. B.; Selkoe, D. J. β-amyloid and a 3-kDa fragment are derived by distinct cellular mechanisms. J. Biol. Chem. 268:3021-3024; 1993.
91. Haass, C.; Hung, A. Y.; Selkoe, D. J.; Teplow, D. B. Mutations associated with a locus for familial Alzheimer's disease result in alternative processing of amyloid β-protein precursor. J. Biol. Chem. 269:17741-17748; 1994.
92. Hadchouel, M.; Farza, H.; Simon, D.; Tiollais, P.; Pourcel, C. Maternal inhibition of hepatitis B surface antigen gene expression in transgenic mice correlates with de novo methylation. Nature 329: 454-456; 1987.
93. Haga, S.; Akai, K.; Ishii, T. Demonstration of microglial cells in and around senile (neuritic) plaques in the Alzheimer brain. Acta Neuropathol. 77:569-575; 1989.
94. Halverson, K.; Fraser, P. E.; Kirschner, D. A.; Lansbury, P. T. Molecular determinants of amyloid deposition in Alzheimer's disease: Conformational studies of synthetic β-protein fragments. Biochemistry 29:2639-2664; 1990.
95. Hasegawa, M.; Arai, T.; Ihara, Y. Immunochemical evidence that fragments of phosphorylated MAPS (MAP1B) are bound to neurofibrillary tangles in Alzheimer's disease. Neuron 4:909-918; 1990.
96. Hayashi, Y.; Kashiwagi, K.; Yoshikawa, K. Protease inhibitors generate cytotoxic fragments from Alzheimer amyloid protein precursor in cDNA-transfected glioma cells. Biochem. Biophys. Res. Commun. 187:1249-1255; 1992.
97. Heald, S. L.; Tilton, R. F.; Hammond, L. J.; Lee, A.; Bayney, R. M.; Kamarck, M. E.; Ramabhadran, T. V.; Dreyer, R. N.; Davis, G.; Unterbeck, A.; Tamburini, P. P. Sequential NMR resonance assignment and structure determination of the Kunitz-type inhibitor domain of the Alzheimer's β-amyloid precursor protein. Biochemistry 30: 10467-10478; 1991.
98. Hendriks, L.; van Duijn, C. M.; Cras, P.; Cruts, M.; Van Hul, W.; van Harskamp, F.; Warren, A.; McInnis, M. G.; Antonarakis, S. E.; Marting, J.-J.; Hofman, A.; Van Broeckhoven, C. Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β-amyloid precursor protein gene. Nat. Genet. 1:218-221; 1992.
99. Heston, L. L.; Orr, H. T.; Rich, S. S.; White, J. A. Linkage of an Alzheimer disease susceptibility locus to markers of human chromosome 21. Am. J. Hum. Genet. 40:449-453; 1991.
100. Higgins, G. A.; Lewis, D. A.; Bahmanyar, S.; Goldgaber, D.; Gajdusek, D. C.; Young, W. G.; Morrison, J. H. Differential regulation of amyloid beta-protein mRNA expression within hippocampal neuronal subpopulations in Alzheimer's disease. Proc. Natl. Acad. Sci. USA 85:1297-1301; 1987.
101. 695, display early Alzheimer's disease-like histopathology. Ann. NY Acad. Sci. 695:224-227; 1993.
102. Higgins, L. S.; Holtzman, D. M.; Rabin, J.; Mobley, W. C.; Cordell, B. Transgenic mouse brain histopathology resembles early Alzheimer's disease. Ann. Neurol. 35:598-607; 1994.
103. 751. Proc. Natl. Acad. Sci. USA 92:4402-4406; 1995.
104. Hoesche, C.; Sauerwald, A.; Veh, R. W.; Krippl, B.; Kilimann, M. W. The 5′ flanking region of the rat synapsin I gene directs neuron-specific and developmentally regulated reporter gene expression in transgenic mice. J. Biol. Chem. 268:26494-26502; 1993.
105. Hoff, P. R.; Bierer, L. M.; Perl, D. P.; Delacourte, A.; Buée, L.; Bouras, C.; Morrison, J. H. Evidence for early vulnerability of the medial and inferior aspects of the temporal lobe in an 82-year-old patient with preclinical signs of dementia. Arch. Neurol. 49:946-953; 1992.
106. Hogan, B.; Constantini, F.; Lacy, E. Manipulating the mouse embryo: A laboratory manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 1986.
107. Howland, D. S.; Hemmendinger, L. M.; Estes, P. S.; Carroll, P. D.; Melloni, R. H.; DeGennaro, L. J. Positive- and negative-acting promoter sequences regulate cell type-specific expression of the rat synapsin I gene. Mol. Brain Res. 11:345-353; 1991.
108. Howland, D. S.; Savage, M. J.; Lang, D. M.; Huntress, F. A.; Wallace, R. E.; Coffee, R.; Pinsker, L. R.; Reaume, A. G.; Trusko, S. P.; Siman, R.; Greenberg, B. D.; Swanson, M. E.; Scott, R. W. Transgenic mouse and rat studies of Alzheimer amyloid precursor protein. Soc. Neurosci. Abstr. 20:1641; 1994.
109. Howland, D. S.; Savage, M. J.; Huntress, F. A.; Wallace, R. E.; Schwartz, D. A.; Loh, T.; Melloni, R. H.; DeGennaro, L. J.; Greenberg, B. D.; Siman, R.; Swanson, M. E.; Scott, R. W. Mutant and native human β-amyloid precursor protein in transgenic mouse brain. Neurobiol. Aging 16:685-699; 1995.
110. Howland, D. S.; Greenberg, B. D.; Savage, M. J.; Siman, R.; Scott, R. W. Authors' response to commentaries. Neurobiol. Aging. 16:715-718; 1995.
111. Hsiao, K. K.; Scott, M.; Foster, D.; Groth, D. F.; DeArmond, S. J.; Prusiner, S. B. Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science 250:1587-1590; 1990.
112. Hung, A. Y.; Koo, E. H.; Haass, C.; Selkoe, D. J. Increased expression of β-amyloid precursor protein during neuronal differentiation is not accompanied by secretory cleavage. Proc. Natl. Acad. Sci. USA 89:9439-9443; 1992.
113. Hyman, B. T.; Van Hoesen, G. W.; Damasio, A. R.; Barnes, C. L. Alzheimer's disease: Cell-specific pathology isolates the hippocampal formation. Science 225:1168-1170; 1984.
114. Hyman, B. T.; Van Hoesen, G. W.; Kromer, L. J.; Damasio, A. R. Perforant pathway changes and the memory impairment of Alzheimer's disease. Ann. Neurol. 20:472-481; 1986.
115. Hyman, B. T.; Van Hoesen, G. W.; Damasio, A. R. Memory-related neural systems in Alzheimer's disease: An anatomic study. Neurology 40:1721-1730; 1990.
116. Hynes, T. R.; Randal, M.; Kennedy, L. A.; Eigenbrot, C.; Kossiakoff, A. A. X-ray crystal structure of the protease inhibitor domain of Alzheimer's amyloid β-protein precursor. Biochemistry 29:10018-10022; 1990.
117. Iannaccone, P. M.; Scarpelli, D. G. Exploring pathogenetic mechanisms using transgenic animals. Ann. Med. 25:131-138; 1993.
118. Ikeda, S.; Allsop, D.; Glenner, G. G. Morphology and distribution of plaque and related deposits in the brains of Alzheimer's disease and control cases: An immunohistochemical study using amyloid β-protein antibody. Lab. Invest. 60:113-122; 1989.
119. Ikeda, K.; Haga, C.; Kosaka, K.; Oyanagi, S. Senile plaque-like structures: Observation of a probably unknown type of senile plaque by periodic-acid methenamine silver (PAM) electron microscopy. Acta Neuropathol. 78:137-142; 1989.
120. Ishii, T.; Kametani, F.; Huge, S.; Sato, M. The immunohistochemical demonstration of subsequences of the precursor of the amyloid A4 protein in senile plaques in Alzheimer's disease. Neuropathol. Appl. Neurobiol. 15:135-147; 1989.
121. Itagaki, S.; McGeer, P. L.; Akiyama, H.; Zhu, S.; Selkoe, D. Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease. J. Neuroimmunol. 24:173-182; 1989.
122. Iwai, A.; Maslliah, E.; Yoshimoto, M.; Ge, N.; Flanagan, L.: Rohan de Silva, H. A.; Kittel, A.; Saitoh, T. The precursor protein on non-Aβ component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system. Neuron 14:467-475; 1995.
123. Iwatsubo, T.; Odaka, A.; Suzuki, N.; Mizusawa, H.; Nukina, N.; Ihara, Y. Visualization of Aβ 42(43) and Aβ 40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ 42(43). Neuron 13:45-53; 1994.
124. Jacobsen, J. S.; Muenkel, H. A.; Blume, A. J.; Vitek, M. P. A novel species-specific RNA related to alternatively spliced amyloid precursor protein mRNAs. Neurobiol. Aging 12:575-583; 1991.
125. Jakobovits, A.; Moore, A. L.; Green, L. L.; Vergara, G. J.; Maynard-Currie, C. E.; Austin, H. A.; Klapholz, S. Germ-line transmission and expression of a human-derived yeast artificial chromosome. Nature 362:255-258; 1993.
126. Jarrett, J. T.; Berger, E. P.; Lansbury, P. T. The carboxy terminus of the β amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimer's disease. Biochemistry 32:4693-4697; 1993.
127. Jarrett, J. T.; Lansbury, P. T. Seeding "one-dimensional crystallization" of amyloid: A pathogenic mechanism in Alzheimer's disease and scrapie? Cell 73:1055-1058; 1993.
128. Joachim, C. L.; Morris, J. H.; Selkoe, D. J. Diffuse senile plaques occur commonly in the cerebellum in Alzheimer's disease. Am. J. Pathol. 135:309-319; 1989.
129. Joachim, C. L.; Mori, H.; Selkoe, D. J. Amyloid β-protein deposition in tissues other than brain in Alzheimer's disease. Nature 341:226-230; 1989.
130. Joachim, C.; Games, D.; Morris, J.; Ward, P.; Frenkel, D.; Selkoe, D. Antibodies to non-beta regions of the beta-amyloid precursor protein detect a subset of senile plaques. Am. J. Pathol. 138:373-384; 1991.
131. 670/671 mutation. FEBS Lett. 354:274-278; 1994.
132. Jucker, M.; Walker, L. C.; Martin, L. J.; Kitt, C. A.; Kleinman, H. K.; Ingram, D. K.; Price, D. L. Age-associated inclusions in normal and transgenic mice. Science 255:1443-1445; 1992.
133. Kammesheidt, A.; Boyce, F. M.; Spanoyannis, A. F.; Cummings, B. J.; Ortegon, M.; Cotman, C.; Vaught, J. L.; Neve, R. L. Deposition of beta/A4 immunoreactivity and neuronal pathology in transgenic mice expressing the carboxyl-terminal fragment of the Alzheimer amyloid precursor protein. Proc. Natl. Acad. Sci. USA 89:10857-10861; 1992.
134. Kang, J.; Lemaire, H. G.; Unterbeck, A.; Salbaum, J. M.; Masters, C. L.; Grzeschik, K. H.; Multhaup, G.; Beyreuther, K.; Müller-Hill, B. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325:733-736; 1987.
135. Kang, J.; Müller-Hill, B. Differential splicing of Alzheimer's disease amyloid A4 precursor RNA in rat tissues: PreA4695 mRNA is predominantly produced in rat and human brain. Biochem. Biophys. Res. Commun. 166:1192-1200; 1990.
136. Karlinsky, H.; Vaula, G.; Haines, J. L.; Ridgley, J.; Bergeron, C.; Mortilla, M.; Tupler, R. G.; Percy, M. E.; Robitaille, Y.; Noldy, N. E.; Yip, T. C. K.; Tanzi, R. E.; Gusella, J. F.; Becker, R.; Berg, J. M.; Crapper-McLachlan, D. R.; St. George-Hyslop, P. H. Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer's disease and a missense mutation in codon 717 of the β-amyloid precursor protein gene. Neurology 42:1445-1453; 1992.
137. Kawabata, S.; Higgins, G. A.; Gordon, J. W. Amyloid plaques, neurofibrillary tangles and neuronal loss in brains of transgenic mice overexpressing a C-terminal fragment of human amyloid precursor protein. Nature 354:476-478; 1991.
138. Kawabata, S.; Higgins, G. A.; Gordon, J. W. Alzheimer's retraction. Nature 356:23; 1992.
139. Kawai, M.; Cras, P.; Perry, G. Serial reconstruction of β-protein amyloid plaques: Relationship to microvessels and size distribution. Brain Res. 592:278-282; 1992.
140. Kemper, T. Neuroanatomical and neuropathological changes in normal aging and in dementia. In: Albert, M. L., ed. Clinical neurology of aging. New York: Oxford University Press: 1984:9-52.
141. Kidd, M. Paired helical filaments in electron microscopy of Alzheimer's disease. Nature 197:192-193; 1963.
142. Kido, H.; Fukutomi, A.; Schilling, J.; Wang, Y.; Cordell, B.; Katunuma, N. Protease-specificity of Kunitz inhibitor domain of Alzheimer's disease amyloid protein precursor. Biochem. Biophys. Res. Commun. 167:716-721; 1990.
143. Kitaguchi, N.; Takahashi, Y.; Tokushima, Y.; Shiojiro, S.; Ito, H. Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature 331:530-532; 1988.
144. Kitaguchi, N.; Takahashi, Y.; Oishi, K.; Shiojiri, S.; Tokushima, Y.; Utsunomiya, T.; Ito, H. Enzyme specificity of proteinase inhibitor region in amyloid precursor protein of Alzheimer's disease: Different properties compared with protease nexin I. Biochim. Biophys. Acta 1038:105-113; 1990.
145. Kitamoto, T.; Ogomori, K.; Tateishi, J.; Prusiner, S. B. Formic acid pretreatment enhances immunostaining of cerebral and systemic amyloids. Lab. Invest. 57:230-236; 1987.
146. König, G.; Mönning, U.; Czech, C.; Prior, R.; Banati, R.; Schreiter-Gasser, U.; Bauer, J.; Masters, C. L.; Beyreuther, K. Identification and differential expression of a novel alternative splice isoform of the βA4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells. J. Biol. Chem. 267:10804-10809; 1992.
147. Koo, E. H.; Sisodia, S. S.; Archer, D. R.; Martin, L. J.; Weidemann, A.; Beyreuther, K.; Fischer, P.; Masters, C. L.; Price, D. L. Amyloid precursor protein undergoes fast anterograde transport. Proc. Natl. Acad. Sci. USA 87:1561-1565; 1990.
148. Kowall, N. W.; Kosik, K. S. Axonal disruption and aberrant localization of tau protein characterize the neuropil pathology of Alzheimer's disease. Ann. Neurol. 22:639-643; 1987.
149. Kowall, N. W.; Beal, M. F.; Busciglio, J.; Duffy, L. K.; Yankner, B. A. An in vivo model for the neurodegenerative effects of β amyloid and protection by substance P. Proc. Natl. Acad. Sci. USA 88: 7247-7251; 1991.
150. Kowall, N. W.; McKee, A. C.; Yankner, B. A.; Beal, M. F. In vivo neurotoxicity of beta-amyloid [β(1-40)] and the β(25-35) fragment. Neurobiol. Aging 13:537-542; 1992.
151. Kuentzel, S. L.; Ali, S. M.; Altman, R. A.; Greenberg, B. D.; Raub, T. J. The Alzheimer β amyloid protein precursor/protease nexin-II is cleaved by secretase in a trans-Golgi secretory compartment in human neuroglioma cells. Biochem. J. 295:367-378; 1993.
152. LaFerla, F. M.; Tinkle, B. T.; Bieberich, C. J.; Haudenschild, C; Jay, G. The Alzheimer's Aβ peptide induces neurodegeneration and apoptotic cell death in transgenic mice. Nat. Genet. 9:21-30; 1995.
153. Lamb, B. T.; Sisodia, S. S.; Lawler, A. M.; Slunt, H. H.; Kitt, C. A.; Kearns, W. G.; Pearson, P. L.; Price, D. L.; Gearhart, J. D. Introduction and expression of the 400 kilobase precursor amyloid protein gene in transgenic mice. Nat. Genet. 5:22-30; 1993.
154. Lannfelt, L.; Bogdanovic, N.; Appelgren, H.; Axelman, K.; Lilius, L.; Hansson, G.; Schenk, D.; Hardy, J.; Winblad, B. Amyloid precursor protein mutation causes Alzheimer's disease in a Swedish family. Neurosci. Lett. 168:254-256; 1994.
155. Lantos, P. L.; Luthert, P. J.; Hanger, D.; Anderton, B. H.; Mullan, M.; Rossor, M. Familial Alzheimer's disease with the amyloid precursor protein position 717 mutation and sporadic Alzheimer's disease have the same cytoskeletal pathology. Neurosci. Lett. 137:221-224; 1992.
156. Lee, V. M.-Y.; Trojanowski, J. Q. The disordered neuronal cytoskeleton in Alzheimer's disease. Curr. Opin. Neurobiol. 2:653-656; 1992.
157. 695 precursor protein of Alzheimer's disease A4 amyloid is encoded by 16 exons. Nucleic Acids Res. 17:517-522; 1989.
158. Levy, E.; Carman, M. D.; Fernandez-Madrid, I. J.; Power, M. D.; Lieberburg, I.; Van Duinen, S. G.; Bots, G. T. A. M.; Luyendijk, W.; Frangione, B. Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science 248:1124-1126; 1990.
159. Lewis, D. A.; Higgins, G. A.; Young, W. G.; Goldgaber, D.; Gajdusek, D. C.; Wilson, M. C.; Morrison, J. H. Distribution of the precursor of amyloid-beta-protein messenger RNA in human cerebral cortex: Relationship to neurofibrillary tangles and neuritic plaques. Proc. Natl. Acad. Sci. USA 85:1691-1695; 1988.
160. Lowery, D. E.; Pasternack, J.; Gonzalez-DeWhitt, P. A.; Zürcher-Neely, H.; Tomich, C.-S. C.; Altman, R. A.; Fairbanks, M. B.; Heinrikson, R. L.; Younkin, S.; Greenberg, B. D. Alzheimer amyloid precursor protein produced by recombinant baculovirus expression: Proteolytic processing and protease inhibitory properties. J. Biol. Chem. 266:19842-19850; 1991.
161. Lu, Q.; Wood, J. G. Functional studies of Alzheimer's disease tau protein. J. Neurosci. 13:508-515; 1993.
162. 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments. Nature 372: 92-94; 1994.
163. Mandybur, T. I.; Chuirazzi, C. C. Astrocytes and the plaques of Alzheimer's disease. Neurology 40:635-639; 1990.
164. Mann, D. M. A. The pathologic association between Down's syndrome and Alzheimer's disease. Mech. Ageing Dev. 43:99-136; 1988.
165. Mann, D. M. A.; Jones, D.; Snowden, J. S.; Neary, D.; Hardy, J. Pathological changes in the brain of a patient with familial Alzheimer's disease having a missense mutation at codon 717 in the amyloid precursor protein gene. Neurosci. Lett. 137:225-228; 1992.
166. Mann, D. M. A.; Jones, D.; South, P. W.; Snowden, J. S.; Neary, D. Deposition of amyloid β protein in non-Alzheimer dementias: Evidence for a neuronal origin of parenchymal deposits of β protein in neurodegenerative disease. Acta Neuropathol. 83:415-419; 1992.
167. Martin, L. J.; Sisodia, S. S.; Koo, E. H.; Cork, L. C.; Dellovade, T. L.; Weidemann, A.; Beyreuther, K.; Masters, C.; Price, D. L. Amyloid precursor protein in aged nonhuman primates. Proc. Natl. Acad. Sci. USA 88:1461-1465; 1991.
168. Maruyama, K.; Terakado, K.; Usami, M.; Yoshikawa, K. Formation of amyloid-like fibrils in COS cells overexpressing part of the Alzheimer amyloid protein precursor. Nature 347:556-569; 1990.
169. Maruyama, K.; Usami, M.; Yamao-Harigaya, W.; Tagawa, K.; Ishiura, S. Mutation of Glu693 to Gln or Val717 to Ile has no effect on the processing of Alzheimer amyloid precursor protein expressed in COS-1 cells by cDNA transfection. Biochem. Biophys. Res. Commun. 132:97-100; 1991.
170. Melloni, R. H.; Hemmendinger, L. M.; Hamos, J. E.; DeGennaro, L. J. Synapsin I gene expression in the adult rat brain with comparative analysis of mRNA and protein in hippocampus. J. Comp. Neurol. 327:507-520; 1993.
171. Miller, D. L.; Papayannopoulos, I. A.; Styles, J.; Bobin, S. A.; Lin, Y. Y.; Biemann, K.; Iqbal, K. Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer's disease. Arch. Biochem. Biophys. 301:41-52; 1993.
172. Mishkin, M. Neural circuitry underlying behavioral deficits in aging. Neurobiol. Aging 14:615-617; 1993.
173. Miyakawa, T.; Shimoji, A.; Kuramoto, R.; Higuchi, Y. The relationship between senile plaques and cerebral blood vessels in Alzheimer's disease and senile dementia. Morphological mechanism of senile plaque production. Virchows Arch. 40:121-129; 1982.
174. Moir, R. D.; Martins, R. N.; Bush, A. I.; Small, D. H.; Milward, E. A.; Rumble, B. A.; Multhaup, G.; Beyreuther, K.; Masters, C. L. Human brain βA4 amyloid protein precursor of Alzheimer's disease: Purification and partial characterization. J. Neurochem. 59:1490-1498; 1992.
175. Mönning, U.; König, G.; Banati, R. B.; Mechler, H.; Czech, C.; Gehrmann, J.; Schreiter-Gasser, U.; Masters, C. L.; Beyreuther, K. Alzheimer βA4-amyloid protein precursor in immunocompetent cells. J. Biol. Chem. 267:23950-23956; 1992.
176. Moran, P. M.; Higgins, L. S.; Cordell, B.; Moser, P. C. Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human β-amyloid precursor protein. Proc. Natl. Acad. Sci. USA 92:5341-5345; 1995.
177. Morris, J. C.; McKeel, D. W.; Storandt, M.; Rubin, E. H.; Price, J. L.; Grant, E. A.; Ball, M. J.; Berg, L. Very mild Alzheimer's disease: Informant-based clinical, psychometric, and pathologic distinction from normal aging. Neurology 41:469-478; 1991.
178. Morris, R. G. M. Spatial localization does not require the presence of local cues. Learn. Motiv. 12:239-249; 1981.
179. Morys, J.; Narkiewicz, O.; Maciejewska, B.; Wegiel, J.; Wisniewski, H. M. Amyloid deposits and loss of neurones in the claustrum of the aged dog. Neuroreport 5:1825-1828; 1994.
180. Mucke, L.; Masliah, E.; Johnson, W. B.; Ruppe, M. D.; Alford, M.; Rochenstein, E. M.; Forss-Petter, S.; Pietropaolo, M.; Mallory, M.; Abraham, C. R. Synaptotrophic effects of human amyloid protein precursors in the cortex of transgenic mice. Brain Res. 666:151-167; 1994.
181. Mullan, M.; Crawford, F.; Axelman, K.; Houlden, H.; Lilus, L.; Winblad, B.; Lannfelt, L. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of β-amyloid. Nat. Genet. 1:345-347; 1992.
182. Mullan, M.; Tsuji, S.; Miki, T.; Katsuya, T.; Naruse, S.; Kaneko, K.; Shimizu, T.; Kojima, T.; Nakano, I,; Ogihara, T.; Miyatake, T.; Ovenstone, I.; Crawford, F.; Goate, A.; Hardy, J.; Roques, P.; Roberts, G.; Luthert, P.; Lantos, P.; Clark, C.; Gaskell, P.; Crain, B.; Roses, A. Clinical comparison of Alzheimer's disease in pedigrees with the codon 717 Val → Ile mutation in the amyloid precursor protein gene. Neurobiol. Aging 14:407-419; 1993.
183. Müller, U.; Cristina, N.; Li, Z.-W.; Wolfer, D. P.; Lipp, H.-P.; Rülicke, T.; Brandner, S.; Aguzzi, A.; Weissmann, C. Behavioral and anatomical deficits in mice homozygous for a modified β-amyloid precursor protein gene. Cell 79:755-765; 1994.
184. Müller-Hill, B.; Beyreuther, K. Molecular biology of Alzheimer's disease. Annu. Rev. Biochem. 57:321-347; 1989.
185. Murphy, G. M.; Murphy, E.; Greenberg, B. D.; Cordell, B.; Eng, L. F.; Ellis, W. G.; Forno, L. S.; Salamat, S. M.; Gonzalez-DeWhitt, P. A.; Lowery, D. E.; Tinklenberg, J. R. Alzheimer's disease: β-Amyloid precursor protein expression in plaques varies among cytoarchitectonic areas of the medial temporal lobe. Neurosci. Lett. 131:100-104; 1991.
186. Murphy, G. M.; Greenberg, B. D.; Ellis, W. G.; Forno, L. S.; Salamat, S. M.; Gonzalez-DeWhitt, P. A.; Lowery, D. E.; Tinklenberg, J. R.; Eng, L. F. Alzheimer's disease β-amyloid precursor protein expression in the nucleus basalis of Meynert. Am. J. Pathol. 141: 357-361; 1992.
187. Murphy, G. M.; Forno, L. S.; Higgins, L.; Scardina, J. M.; Eng, L. F.; Cordell, B. Development of a monoclonal antibody specific for the COOH-terminal of β-amyloid 1-42 and its immunohistochemical reactivity in Alzheimer's disease and related disorders. Am. J. Pathol. 144:1082-1088; 1994.
188. Murrell, J.; Farlow, B.; Ghetti, B.; Benson, M. D. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science 254:97-99; 1991.
189. Namba, Y.; Tomonaga, M.; Kawasaki, H.; Otomo, E.; Ikeda, K. Apolipoprotein E immunoreactivity in cerebral deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jacob disease. Brain Res. 541:163-166; 1991.
190. Narindrasorasak, S.; Lowery, D.; Gonzalez-DeWhitt, P. A.; Poorman, R. A.; Greenberg, B.; Kisilevsky, R. High affinity interactions between the Alzheimer's β-amyloid precursor proteins and the basement membrane form of heparan sulphate proteoglycan. J. Biol. Chem. 266:12878-12883; 1991.
191. Narindrasorasak, S.; Altman, R. A.; Gonzalez-DeWhitt, P.; Greenberg, B. D.; Kisilevsky, R. Further studies on basement membrane protein: Alzheimer amyloid precursor protein interactions. Lab. Invest. 72:272-282; 1994.
192. Naruse, S.; Igarashi, S.; Kobayashi, H.; Aoki, K.; Inuzuka, T.; Kaneko, K.; Shimizu, T.; Iihara, K.; Kojima, T.; Miyatake, T.; Tsuji, S. Mis-sense mutation Val→Ile in exon 17 of amyloid precursor protein gene in Japanese familial Alzheimer's disease. Lancet 337: 978-979; 1991.
193. Nelson, P. T.; Greenberg, S. G.; Saper, C. B. Neurofibrillary tangles in the cerebral cortex of sheep. Neurosci. Lett. 170:187-190; 1994.
194. Neve, R. L.; Finch, E. A.; Dawes, L. R. Expression of the Alzheimer amyloid precursor protein gene transcripts in the human brain. Neuron 1:669-677; 1988.
195. Ohyagi, Y.; Takahashi, K.; Kamegai, M.; Tabira, T. Developmental and differential expression of beta amyloid protein precursor mRNAs in mouse brain. Biochem. Biophys. Res. Commun. 167:54-60; 1990.
196. Ötvös, L.; Szendrei, G. I.; Lee, V. M.-Y.; Mantsch, H. H. Human and rodent Alzheimer β-amyloid peptides acquire distinct conformations in membrane-mimicking solvents. Eur. J. Biochem. 211:249-257; 1993.
197. Palmert, M. R.; Podlisny, M. B.; Witker, D. S.; Oltersdorf, T.; Younkin, L. H.; Selkoe, D. J.; Younkin, S. G. Antisera to an amino-terminal peptide detect the amyloid protein precursor of Alzheimer's disease and recognize senile plaques. Biochem. Biophys. Res. Commun. 156:432-437; 1988.
198. Palmert, M. R.; Golde, T. E.; Cohen, M. L.; Kovacs, D. M.; Tanzi, R. E.; Gusella, J. F.; Usiak, M. F.; Younkin, L. H.; Younkin, S. G. Amyloid protein precursor messenger RNAs: Differential expression in Alzheimer's disease. Science 241:1080-1084; 1988.
199. Palmert, M. R.; Podlisny, M. B.; Witker, D. S.; Oltersdorf, T.; Younkin, L. H.; Selkoe, D. J.; Younkin, S. G. The β-amyloid protein precursor of Alzheimer disease has soluble derivatives found in human brain and cerebrospinal fluid. Proc. Natl. Acad. Sci. USA 86: 6338-6342; 1989.
200. Palmiter, R. D.; Brinster, R. L. Germ-line transformation of mice. Annu. Rev. Genet. 20:465-499; 1986.
201. Palmiter, R. D.; Sandgren, E. P.; Avarbock, M. R.; Allen, D. D.; Brinster, R. L. Heterologous introns can enhance expression of transgenes in mice. Proc. Natl. Acad. Sci. USA 88:478-482; 1991.
202. Pappolla, M. A.; Omar, R. A.; Sambamurti, K.; Anderson, J. P.; Robakis, N. K. The genesis of the senile plaque: Further evidence in support of its neuronal origin. Am. J. Pathol. 141:1151-1159; 1992.
203. 1-amichymotrypsin mRNA. Am. J. Pathol. 135:827-834; 1989.
204. Pasternack, J. M.; Palmert, M. R.; Usiak, M.; Wang, R.; Zürcher-Neely, H.; Gonzalez-DeWhitt, P. A.; Fairbanks, M. B.; Chung, T.; Blades, C.; Heinrikson, R. L.; Greenberg, B. D.; Cotter, R. J.; Younkin, S. G. Alzheimer's disease and control brain contain soluble derivatives of the β amyloid protein precursor that end within the amyloid protein region. Biochemistry 31:10936-10940; 1992.
205. Pearson, R. C. A.; Esiri, M. M.; Hiorns, R. W.; Wilcock, G. K.; Powell, T. P. S. Anatomical correlates of the distribution of the pathologic changes in the neocortex in Alzheimer's disease. Proc. Natl. Acad. Sci. USA 82:4531-4534; 1985.
206. Pearson, B. E.; Choi, T. K. Expression of the human beta-amyloid precursor protein gene from a yeast artificial chromosome in transgenic mice. Proc. Natl. Acad. Sci. USA 90:10578-10582; 1993.
207. Pericak-Vance, M. A.; Bebout, J. L.; Gaskell, P. C.; Yamaoka, L. H.; Hung, W.-Y.; Alberts, M. J.; Walker, A. P.; Bartlett, R. J.; Haynes, C. A.; Welsh, K. A.; Earl, N. L.; Heyman, A.; Clark, C. M.; Roses, A. D. Linkage studies in familial Alzheimer's disease: Evidence for chromosome 19 linkage. Am. J. Hum. Genet. 48:1034-1050; 1991.
208. Perry, G.; Siedlak, S. L.; Richy, P.; Price, D. L.; Struble, R. G.; Whitehouse, P. J.; Kitt, C. A.; Cork, L. C.; Walker, L. C.; Casanova, M. F. Alzheimer's disease: A multisystem disorder. In: Martin, J. B.; Barchas, J. D., eds. Neuropeptides in Neurologic and Psychiatric Disease. New York: Raven Press; 1986:209-214.
209. Perry, G.; Lipphardt, S.; Mulvihill, P.; Kancherla, M.; Mijares, M.; Autilio-Gambetti, L.; Gambetti, P.; Sharma, S.; Maggiora, L.; Cornette, J.; Lobl, T.; Greenberg, B. Amyloid precursor protein in senile plaques of Alzheimer disease. Lancet ii:746; 1988.
210. Perry, G.; Siedlak, S. L.; Richey, P.; Mulvihill, P.; Kawai, M.; Cras, P.; Kalaria, R.; Galloway, P.; Scardina, J. M.; Cordell, B.; Greenberg, B. D.; Ledbetter, S.; Gambetti, P. Association of a heparan sulfate protcoglycan with the neurofibrillary pathology of Alzheimer Disease. J. Neurosci. 11:3679-3683; 1991.
211. 1-antichymotrypsin in cerebral and systemic amyloid. J. Neuropathol. Exp. Neurol. 49:41-48; 1990.
212. Podlisny, M. B.; Tolan, D. R.; Selkoe, D. J. Homology of the amyloid beta protein precursor in monkey and human supports a primate model for beta amyloidosis in Alzheimer's disease. Am. J. Pathol. 138:1423-1435; 1991.
213. Podlisny, M. B.; Stephenson, D. T.; Frosch, M. P.; Lieberburg, I.; Clemens, J. A.; Selkoe, D. J. Synthetic amyloid β-protein fails to produce specific neurotoxicity in monkey cerebral cortex. Neurobiol. Aging 13:561-567; 1992.
214. Podlisny, M. B.; Stephenson, D. T.; Frosch, M. P.; Tolan, D. R.; Lieberburg, I.; Clemens, J. A.; Selkoe, D. J. Microinjection of synthetic amyloid β-protein in monkey cerebral cortex fails to produce acute neurotoxicity. Am. J. Pathol. 142:17-24; 1993.
215. Ponte, P.; Gonzalez-DeWhitt, P.; Schilling, J.; Miller, J.; Hsu, D.; Greenberg, B.; Davis, K.; Wallace, W.; Lieberburg, I.; Fuller, F.; Cordell, B. A new A4 amyloid mRNA contains a domain homologous to serine protease inhibitors. Nature 331:525-527; 1988.
216. Potempska, A.; Styles, J.; Mehta, P.; Kim, K. S.; Miller, D. L. Purification and tissue level of the β-amyloid peptide precursor of rat brain. J. Biol. Chem. 266:8464-8469; 1991.
217. Prelli, F.; Castano, F. E.; Glenner, G. G.; Frangione, B. Differences between vascular and plaque core amyloid in Alzheimer's disease. J. Neurochem. 51:648-651; 1988.
218. Price, D. L.; Cork, L. C.; Struble, R. G. Neuropathological, neurochemical, and behavioral studies of the aging nonhuman primate. In: Davis, R. T.; Leathers, C. W., eds. Behavior and Pathology of Aging in rhesus monkeys. New York: Alan R. Liss; 1985:113-135.
219. Price, D. L.; Walker, L. C.; Martin, L. J.; Sisodia, S. S. Amyloidosis in aging and Alzheimer's disease. Am. J. Pathol. 141:767-772; 1992.
220. Price, J. L.; Davis, P. B.; Morris, J. C.; White, D. L. The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease. Neurobiol. Aging 12:295-312; 1991.
221. Querfurth, H. W.; Selkoe, D. J. Calcium ionophore increases amyloid β peptide production by cultured cells. Biochemistry 33:4550-4561; 1994.
222. Quon, D.; Wang, Y.; Catalano, R.; Scardina, J. M.; Murakami, K.; Cordell, B. Formation of beta-amyloid protein deposits in brains of transgenic mice. Nature 352:239-241; 1991.
223. Rebeck, G. W.; Reiter, J. S.; Strickland, D. K.; Hyman, B. T. Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions. Neuron 11:575-580; 1993.
224. Reusche, E. Silver staining of senile plaques and neurofibrillary tangles in paraffin sections: A simple and effective method. Pathol. Res. Pract. 187:1045-1049; 1991.
225. Roher, A. E.; Lowenson, J. D.; Clarke, S.; Wolkow, C.; Wang, R.; Cotter, R. J.; Reardon, I. M.; Zürcher-Neely, H. A.; Heinrikson, R. L.; Ball, M. J.; Greenberg, B. D. Structural alterations in the peptide backbone of β-amyloid core protein may account for its deposition and stability in Alzheimer's disease. J. Biol. Chem. 268:3072-3083; 1993.
226. Roher, A. E.; Lowenson, J. D.; Clarke, S.; Woods, A. S.; Cotter, R. J.; Gowing, E.; Ball, M. J. β-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: Implications for the pathology of Alzheimer disease. Proc. Natl. Acad. Sci. USA 90:10836-10840; 1993.
227. Roher, A. E.; Palmer, K. C; Yurewicz, E. C.; Ball, M. J.; Greenberg, B. D. Morphological and biochemical analyses of amyloid plaque core proteins purified from Alzheimer disease brain tissue. J. Neurochem. 61:1916-1926; 1993.
228. Roth, M. The association of clinical and neurological findings and its bearing on the classification and aetiology of Alzheimer's disease. Br. Med. Bull. 42:42-50; 1986.
229. Rumble, B.; Retallack, R.; Hilbich, C.; Simms, G.; Multhaup, G.; Martins, R.; Hockey, A.; Montgomery, P.; Beyreuther, K.; Masters, C. L. Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease. N. Engl. J. Med. 320:1446-1452; 1989.
230. Rush, D. K.; Aschmies, S.; Merriman, M. C. Intracerebral β-amyloid(25-35) produces tissue damage: Is it neurotoxic? Neurobiol. Aging 13:591-594; 1992.
231. Russo, A. F.; Crenshaw, E. B.; Lira, S. A.; Simmons, D. M.; Swanson, L. W.; Rosenfeld, M. G. Neuronal expression of chimeric genes in transgenic mice. Neuron 1:311-320; 1988.
232. Sandhu, F. A.; Salim, M.; Zain, S. B. Expression of the human beta-amyloid protein of Alzheimer's disease specifically in the brains of transgenic mice. J. Biol. Chem. 266:21331-21334; 1991.
233. Sapienza, C.; Peterson, A. C.; Rossant, J.; Balling, R. Degree of methylation of transgenes is dependent on gamete of origin. Nature 328:251-254; 1987.
234. Sasahara, M.; Fries, J. W.; Raines, E. W.; Gown, A. M.; Westrum, L. E.; Frosch, M. P.; Bonthron, D. T.; Ross, R.; Collins, T. PDGF B-chain in neurons of the central nervous system, posterior pituitary, and in a transgenic model. Cell 64:217-227; 1991.
235. Saunders, A. M.; Strittmatter, W. J.; Schmechel, D.; St. George-Hyslop, P. H.; Pericak-Vance, M. A.; Joo, S. H.; Rosi, B. L.; Gusella, J. F.; Crapper-MacLachlan, D. R.; Growden, J.; Alberts, M. J.; Hulette, C.; Crain, B.; Goldgaber, D.; Roses, A. D. Association of apolipoprotein E allele e4 with late-onset familial and sporadic Alzheimer's disease. Neurology 43:1467-1472; 1993.
236. Savage, M. J.; Pinsker, L.; Mistretta, S.; Emmons, T.; Kawooya, J. K.; Siman, R.; Greenberg, B. D. Elevated Aβ levels in Alzheimer's disease brain are associated with selective accumulation of Aβ42 in parenchymal amyloid plaques and both Aβ40 and Aβ42 in cerebrovascular deposits. Amyloid: Int. J. Exp. Clin. Invest. 2:234-240; 1995.
237. Schedl, A.; Beerman, F.; Thies, E.; Montoliu, L.; Kelsey, G.; Schütz, G. Transgenic mice generated by pronuclear injection of a yeast artificial chromosome. Nucleic Acids Res. 20:3073-3077; 1992.
238. Schellenberg, G. D.; Pericak-Vance, M. A.; Wijsman, E. M.; Moore, D. K.; Gaskell, P. C.; Yamaoka, L. A.; Bebout, J. L.; Anderson, L.; Welsh, K. A.; Clark, C. M.; Martin, G. M.; Roses, A. D.; Bird, T. D. Linkage analysis of familial Alzheimer disease, using chromosome 21 markers. Am. J. Hum. Genet. 48:563-583; 1991.
239. Schellenberg, G. D.; Bird, T. D.; Wijsman, E. M.; Orr, H. T.; Anderson, L.; Nemens, E.; White, J. A.; Bonnycastle, L.; Weber, J. L.; Alonson, M. E.; Potter, H.; Heston, L. L.; Martin, G. M. Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14. Science 258:668-671; 1992.
240. Schellenberg, G. D.; Boehnke, M.; Wijsman, E. M.; Moore, D. K.; Martin, G. M.; Bird, T. D. Genetic association and linkage analysis of the apolipoprotein CII locus and familial Alzheimer's disease. Ann. Neurol. 31:223-227; 1992.
241. Schlossmacher, M. G.; Ostaszewski, B. L.; Hecker, L. I.; Celi, A.; Haass, C.; Chin, D.; Lieberburg, I.; Furie, B. C.; Furie, B.; Selkoe, D. J. Detection of distinct isoform patterns of the β-amyloid precursor protein in human platelets and lymphocytes. Neurobiol. Aging 13:421-434; 1992.
242. Schmaier, A. H.; Dahl, L. D.; Rozemuller, A. J. M.; Roos, R. A. C.: Wagner, S. L.; Chung, R.; Van Nostrand, W. E. Protease nexin-2/ amyloid β protein precursor: A tight binding inhibitor of coagulation factor IXa. J. Clin. Invest. 92:2540-2545; 1993.
243. Schmechel, D. E.; Saunders, A. M.; Strittmatter, W. J.; Crain, B. J.; Hulette, C. M.; Joo, S. H.; Pericak-Vance, M. A.; Goldgaber, D.; Roses, A. D. Increased amyloid β-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer's disease. Proc. Natl. Acad. Sci. USA 90:9649-9653; 1993.
244. Scott, R. W.; Howland, D. S.; Greenberg, B. D.; Savage, M. J.; Swanson, M. E. Strategies in the development of transgenic animal models for β-amyloid-related neuropathologies of Alzheimer's disease. In: Monastersky, G. M.; Robl, J. M., eds. Strategies in transgenic animal science. Washington, DC: American Society for Microbiology Press; 1994:145-180.
245. Selkoe, D. J.; Bell, D. S.; Podlisny, M. B.; Price, D. L.; Cork, L. C. Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease. Science 235:873-877; 1987.
246. Selkoe, D. J. Molecular pathology of amyloidogenic proteins and the role of vascular amyloidosis in Alzheimer's disease. Neurobiol. Aging 10:387-395; 1989.
247. Selkoe, D. J. The molecular pathology of Alzheimer's disease. Neuron 6:487-498; 1991.
248. Selkoe, D. J. Physiological production of the β-amyloid protein and the mechanism of Alzheimer's disease. Trends Neurol. Sci. 16:403-409; 1993.
249. Seubert, P. Vigo-Pelfrey, C.; Esche, F.; Lee, M.; Dovey, H.; Davis, D.; Sinha, S.; Schlossmacher, M.; Whaley, J.; Swindlehurst, C.; McCormack, R.; Wolfert, R.; Selkoe, D.; Lieberburg, I.; Schenk, D. Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids. Nature 359:325-327; 1992.
250. Seubert, P.; Oltersdorf, T.; Lee, M. G.; Barbour, R.; Blomquist, C.; Davis, D. L.; Bryant, K.; Fritz, L. C.; Galasko, D.; Thal, L. J.; Lieberburg, I.; Schenk, D. B. Secretion of β-amyloid precursor protein cleaved at the amino terminus of the β-amyloid peptide. Nature 361: 260-263; 1993.
251. Sherrington, R.; Rogaev, E. I.; Liang, Y.; Rogaeva, E. A.; Levesque, G.; Ikeda, M.; Chi, H.; Lin, C.; Li, G.; Holman, K.; Tsuda, T.; Mar, L.; Foncin, J.-F.; Bruni, A. C.; Montesi, M. P.; Sorbi, S.; Rainero, I.; Pinessi, L.; Nee, L.; Chumakov, I.; Pollen, D.; Brookes, A.; Sanseau, P.; Polinsky, R. J.; Wasco, W.; Da Silva, H. A. R.; Haines, J. L.; Pericak-Vance, M. A.; Tanzi, R. E.; Roses, A. D.; Fraser, P. E.; Rommens, J. M.; St. George-Hyslop, P. H. Cloning of a gene bearing missense mutations in early onset familial Alzheimer's disease. Nature 375:754-760; 1995.
252. 1-antichymotrypsin. Proc. Natl. Acad. Sci USA 90:6825-6828; 1993.
253. Shivers, B. D.; Hilbich, C.; Multhaup, G.; Salbaum, M.; Beyreuther, K.; Seeburg, P. H. Alzheimer's disease amyloidogenic glycoprotein: Expression pattern in rat suggests a role in cell contact. EMBO J. 7:1365-1370; 1988.
254. Shoji, M.; Golde, T. E.; Ghiso, J.; Cheung, T. T.; Estus, S.; Shaffer, L. M.; Cai, X. D.; McKay, D. M.; Tinter, R.; Frangione, B.; Younkin, S. G. Production of the Alzheimer amyloid β protein by normal proteolytic processing. Science 258:126-129; 1992.
255. Siman, R.; Card, J. P.; Nelson, R. B.; Davis, L. G. Expression of β-amyloid precursor protein in reactive astrocytes following neuronal damage. Neuron 3:275-285; 1989.
256. Siman, R.; Mistretta, S.; Durkin, J. T.; Savage, M. J.; Loh, T.; Trusko, S.; Scott, R. W. Processing of the β-amyloid precursor: Multiple proteases generate and degrade potentially amyloidogenic fragments. J. Biol. Chem. 268:16602-16609; 1993.
257. Siman, R.; Greenberg, B. D. Alzheimer's disease, In: Pullan, L.; Patel, J., eds. Neurotherapeutics: emerging strategies. Totowa, NJ: Humana Press; 1995:389-428.
258. Siman, R.; Durkin, J. T.; Husten, E. J.; Savage, M. J.; Murthy, S.; Mistretta, S.; Chatterjee, S.; Rotella, D. P.; Dembofsky, B.; Poorman, R.; Greenberg, B. D. Genesis and degradation of Aβ protein by cultured human neuroblastoma cells. In: Iqbal, K.; Mortimer, J. A.; Winblad, B.; Wisniewski, H. M., eds. Research advances in Alzheimer's disease and related disorders. Chichester: J. Wiley and Sons, Ltd.; 1995:675-684.
259. Simonet, W. S.; Bucay, N.; Lauer, S. J.; Taylor, J. M. A far-downstream hepatocyte-specific control region directs expression of the linked human apolipoprotein E and C-I genes in transgenic mice. J. Biol. Chem. 268:8221-8229; 1993.
260. Simons, M.; Ikonen, E.; Tienari, P. J.; Cid-Arregui, A.; Mönning, U.; Beyreuther, K.; Dotti, C. G. Intracellular routing of human amyloid protein precursor: Axonal delivery followed by transport to the dendrites. J. Neurosci. Res. 41:121-128; 1995.
261. Sinha, S.; Dovey, H. F.; Seubert, P.; Ward, P. J.; Blacher, R. W.; Blaber, M.; Bradshaw, R. A.; Arici, M.; Mobley, W. C.; Lieberburg, I. The protease inhibitory properties of the Alzheimer's β-amyloid precursor protein. J. Biol. Chem. 265:8983-8985; 1990.
262. Sinha, S.; Knops, J.; Esch, F.; Moyer, E. D.; Oltersdorf, T. Conversion of the Alzheimer's β-amyloid precursor protein (APP) Kunitz domain into a potent human neutrophil elastase inhibitor. J. Biol. Chem. 266:21011-21013; 1991.
263. Sipe, J. D.; Carreras, I.; Gonnerman, W. A.; Cathcart, E. S.; de Beer, M. C.; de Beer, F. C. Characterization of the inbred CE/J mouse strain as amyloid resistant. Am. J. Pathol. 143:1480-1485; 1993.
264. Sisodia, S. S.; Koo, E. H.; Beyreuther, K.; Umerbeck, A.; Price, D. L. Evidence that β-amyloid protein in Alzheimer's disease is not derived by normal processing. Science 248:492-495; 1990.
265. Sisodia, S. S.; Koo, E. H.; Hoffman, P. N.; Perry, G.; Price, D. L. Identification and transport of full-length amyloid precursor proteins in rat peripheral nervous system. J. Neurosci. 13:3136-3142; 1993.
266. Small, J. A.; Scangos, G. A.; Cork, L.; Jay, G.; Khoury, G. The early region of human papovavirus JC induces dysmyelination in transgenic mice. Cell 46:13-18; 1986.
267. a-inhibitor, a form of Alzheimer amyloid precursor protein. Science 248:1126-1128; 1990.
268. Smyth, M. D.; Kesslak, J. P.; Cummings, B. J.; Cotman, C. W. Analysis of brain injury following intrahippocampal administration of β-amyloid in streptozotocin-treated rats. Neurobiol. Aging 15: 153-159; 1994.
269. Snow, A. D.; Mar, H.; Nochlin, D.; Kimata, K.; Sato, M.; Suzuki, S.; Hassell, J.; Wight, T. N. The presence of heparan sulfate proteoglycans in the neuritic plaques and congophilic angiopathy in Alzheimer's disease. Am. J. Pathol. 133:456-463; 1988.
270. Snow, A. D.; Sekiguchi, R.; Nochlin, D.; Fraser, P.; Kimata, K.; Mizutani, A.; Arai, M.; Schreier, W. A.; Morgan, D. G. An important role of heparan sulfate proteoglycan (Perlecan) in a model system for the deposition and persistence of fibrillar Aβ-amyloid in rat brain. Neuron 12:129-234; 1994.
271. Spillantini, M. G.; Hunt, S. P.; Ulrich, J.; Goedert, M. Expression and cellular localization of amyloid β-protein precursor transcripts in normal human brain and in Alzheimer's disease. Mol. Brain Res. 6:143-150; 1989.
272. Standaert, D.; Lee, V. M.-Y.; Greenberg, B. D.; Lowery, D. E.; Trojanowski, J. Q. Molecular features of hypothalamic plaques in Alzheimer's Disease. Am. J. Pathol. 139:681-691; 1991.
273. Stein-Behrens, B.; Adams, K.; Yeh, M.; Sapolsky, R. Failure of beta-amyloid protein fragment 25-35 to cause hippocampal damage in the rat. Neurobiol. Aging 13:577-579; 1992.
274. Stephenson, D. T.; Clemens, J. A. In vivo effects of β-amyloid implants in rodents: Lack of potentiation of damage associated with transient global forebrain ischemia. Brain Res. 586:235-246; 1992.
275. St. George-Hyslop, P.; Haines, J.; Rogaev, E.; Mortilla, M.; Vaula, G.; Pericak-Vance, M.; Foncin, J.-F.; Montesi, M.; Bruni, A.; Sorbi, S.; Rainero, I.; Pinessi, L.; Pollen, D.; Polinsky, R.; Nee, L.; Kennedy, J.; Vacciardi, F.; Rogaeva, E.; Liang, Y.; Alexandrova, N.; Lukiw, W.; Schlumpf, K.; Tanzi, R.; Tsuda, T.; Fairer, L.; Cantu, J.-M.; Duara, R.; Amaducci, L.; Bergamini, L.; Gusella, J.; Roses, A.; Crapper-McLachlan, D. Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14. Nat. Genet. 2:330-334; 1992.
276. 1(I) collagen locus. Science 259:1904-1907; 1993.
277. Strittmatter, W. J.; Saunders, A. M.; Schmechel, D,; Pericak-Vance, M.; Enghild, J.; Salvesen, G. S.; Roses, A. D. Apolipoprotein E: High-avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer's disease. Proc. Natl. Acad. Sci. USA 90:1977-1981; 1993.
278. Struble, R. G.; Price, D. J.; Cork, L. C.; Price, D. L. Senile plaques in cortex of aged normal monkeys. Brain Res. 361:267-275; 1985.
279. 717) mutants. Science 264: 1336-1340; 1994.
280. Suzuki, N.; Cheung, T. T.; Cai, X.-D.; Ötvös, L.; Gillespie, S. L.; Ho, L.; Eckman, C. B.; Golde, T. E.; Younkin, S. G. Factors affecting production of secreted amyloid protein ending at Aβ42,43. Soc. Neurosci. Abstr. 20:437; 1994.
281. Suzuki, N.; Iwatsubo, T.; Odaka, A.; Ishibashi, Y.; Kitada, C.; Ihara, Y. High tissue content of soluble Aβ1-40 is linked to cerebral amyloid angiopathy. Am. J. Pathol. 145:452-460; 1994.
282. Swanson, L. W.; Simmons, D. M.; Arriza, J.; Hammer, R.; Brinster, R.; Rosenfeld, M. G.; Evans, R. M. Novel developmental specificity in the nervous system of transgenic animals expressing growth hormone fusion genes. Nature 317:363-366; 1985.
283. Tagliavini, F.; Giaccone, G.; Frangione, B.; Bugiani, O. Preamyloid deposits in the cerebral cortex of patients with Alzheimer's disease and nondemented individuals. Neurosci. Lett. 93:191-196; 1988.
284. Tanzi, R. E.; Gusella, J. F.; Watkins, P. C.; Bruns, G. A. P.; St. George-Hyslop, P.; Van Keuren, M. L.; Patterson, C.; Pagan, S.; Kurnit, D. M.; Neve, R. L. Amyloid β protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 235:880-884; 1987.
285. Tanzi, R. E.; McClatchey, A. I.; Lamperti, E. D., Villa-Komaroff, L.; Gusella, J. F.; Neve, R. L. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature 331:528-530; 1988.
286. Tanzi, R. E.; Vaula, G.; Romano, D. M.; Mortilla, M.; Huang, T. L.; Tupler, R. G.; Wasco, W.; Hyman, B. T.; Haines, J. L.; Henkins, B. J.; Kalaitsidaki, M.; Warren, A. C.; McInnis, M. C.; Antonarakis, S. E.; Karlinsky, H.; Percy, M. E.; Connor, L.; Growdon, J.; Crapper-McLachlan, D. R.; Gusella, J. F.; St. George-Hyslop, P. H. Assessment of amyloid β-protein precursor gene mutations in a large set of familiar and sporadic Alzheimer disease cases. Am. J. Hum. Genet. 51:273-282; 1992.
287. Tanzi, R. E. Promising animal model of Alzheimer's disease. N. Engl. J. Med. 332:1512-1513; 1995.
288. Terry, R. D. The fine structure of neurofibrillary tangles in Alzheimer's disease. J. Neuropathol. Exp. Neurol. 22:629-641; 1963.
289. Terry, R. D.; Masliah, E.; Salmon, D. P.; Butters, N.; DeTeresa, R.; Hill, R.; Hansen, L. A.; Katzman, R. Physical basis of cognitive alterations in Alzheimer's disease: Synapse loss is the major correlate of cognitive impairment. Ann. Neurol. 30:572-580; 1991.
290. Uéda, K.; Fukushima, H.; Masliah, E.; Xia, Y.; Iwai, A.;
291. Van Broeckhoven, C.; Genthe, A. M.; Vandenberghe, A.; Horsthemke, B.; Backhovens, H.; Raeymaekers, P.; Van Hui, W.; Wehnert, A.; Gheuens, J.; Cras, P.; Bruyland, M.; Martin, J. J.; Salbaum, M.; Multhaup, G.; Masters, C. L.; Beyreuther, K.; Gurling, H. M. D.; Mullan, M. J.; Holland, A.; Barton, A.; Irving, N.; Williamson, R.; Richards, S. J.; Hardy, J. A. Failure of familial Alzheimer's disease to segregate with the A4-amyloid gene in several European families. Nature 329:153-155; 1987.
292. van Duinen, S. G.; Castano, E. M.; Prelli, F.; Bots, G. T. A. B.; Luyendijk, W.; Frangione, B. Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease. Proc. Natl. Acad. Sci. USA 84:5991-5994; 1987.
293. Van Nostrand, W. E.; Wagner, S. L.; Farrow, J. S.; Cunningham, D. D. Immunopurification and protease inhibitory properties of protease nexin-2/amyloid β-protein precursor. J. Biol. Chem. 265:9591-9594; 1990.
294. Vinters, H. V.; Partridge, W. M.; Secor, D. L.; Ishii, N. Immunohistochemical study of cerebral amyloid angiopathy II. Am. J. Pathol. 133:150-152; 1988.
295. Wagner, S. L.; Siegel, R. S.; Vedvick, T. S.; Raschke, W. C.; Van Nostrand, W. E. High level expression, purification, and characterization of the Kunitz-type protease inhibitor domain of protease nexin-2/amyloid β-protein precursor. Biochem. Biophys. Res. Commun. 186:1138-1145; 1992.
296. Waite, J.; Cole, G. M.; Frautschy, S. A.; Connor, D. J.; Thai, L. J. Solvent effects on beta protein toxicity in vivo. Neurobiol. Aging 13:595-599; 1992.
297. Walker, L. C.; Kitt, C. A.; Schwam, E.; Buckwald, B.; Garcia, F.; Sepinwall, J.; Price, D. L. Senile plaques in aged squirrel monkeys. Neurobiol. Aging 8:291-296; 1987.
298. Walker, L. C.; Kitt, C. A.; Struble, R. G.; Wagster, M. V.; Price, D. L. Cork, L. C. The neural basis of memory decline in aged monkeys. Neurobiol. Aging 9:657-666: 1988.
299. Walker, L. C.; Masters, C.; Beyreuther, K.; Price, D. L. Amyloid in the brains of aged squirrel monkeys. Acta Neuropathol. 80:381-387; 1990.
300. Wang, Z.; Liu, R.-H.; Reddy, V. K.; Barnes, C. D. Hippocampal β-amyloid reduces locus coeruleus glutamate and tyrosine hydroxylase. Brain Res. Bull. 35:485-491; 1994.
301. Weidemann, A.; König, G.; Bunke, D.; Fischer, P.; Salbaum, J. M.; Masters, C. L.; Beyreuther, K. Identification, biogenesis and localization of precursor of Alzheimer's disease A4 amyloid protein. Cell 57:115-126; 1989.
302. Wertkin, A. M.; Turner, R. S.; Pleasure, S. J.; Golde, T. E.; Younkin, S. G.; Trojanowski, J. Q.; Lee, V. M.-Y. Human neurons derived from a teratocarcinoma cell line express solely the 695-amino acid amyloid precursor protein and produce intracellular β-amyloid or A4 peptides. Proc. Natl. Acad. Sci. USA 90:9513-9517: 1993.
303. Winkler, J.; Connor, D. J.; Frautschy, S. A.; Behl, C; Waite, J. J.; Cole, G. M.; Thal, L. J. Lack of long-term effects after β-amyloid protein injections in rat brain. Neurobiol. Aging 15:601-607; 1994.
304. Wirak, D. O.; Bayney, R.; Kundel, C. A.; Lee, A.; Scangos, G. A.; Trapp, B. D.; Unterbeck, A. J. Regulatory region of human amyloid precursor protein (APP) gene promotes neuron-specific gene expression in the CNS of transgenic mice. EMBO J. 10:289-296; 1991.
305. Wirak, D. O.; Bayney, R.; Ramabhadran, T. V.; Fracasso, R. P.; Hart, J. T.; Hauer, P. E.; Hsiau, P.; Pekar, S. K.; Scangos, G. A.; Trapp, B. D.; Unterbeck, A. Deposits of amyloid β protein in the central nervous system of transgenic mice. Science 253:323-325; 1991.
306. Wirak, D.; Bayner, R.; Ramabhadran, T. C.; Fracasso, R. P.; Hart, J. T.; Hauer, P. E.; Hsiau, P.; Pekar, S. K.; Scangos, G. A.; Trapp, B. D.; Unterbeck, A. J. Science 255:1445; 1992.
307. Wisniewski, H. M.; Ghetti, B.; Terry, R. D. Neuritic (senile) plaques and filamentous changes in aged Rhesus monkeys. J. Neuropathol. Exp. Neurol. 32:566-584; 1973.
308. Wisniewski, H. M.; Wegiel, J. Spatial relationships between astrocytes and classical plaque components. Neurobiol. Aging 12:593-600; 1991.
309. Wisniewski, T.; Ghiso, J.; Frangione, B. Peptides homologous to the amyloid protein of Alzheimer's disease containing a glutamine for glutamic acid substitution have accelerated amyloid fibril formation. Biochem. Biophys. Res. Commun. 179:1247-1254; 1991.
310. Wisniewski, T.; Golabek, A.; Matsubara, E.; Ghiso, J.; Frangione, B. Apolipoprotein E: Binding to soluble Alzheimer's β-amyloid. Biochem. Biophys. Res. Commun. 192:359-365; 1993.
311. Wisniewski, T.; Castano, E. M.; Golabek, A.; Vogel, T.; Frangione, B. Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro. Am. J. Pathol. 145:1030-1035; 1994.
312. Xu, Z.; Cork, L. C.; Griffin, J. W.; Cleveland, D. W. Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell 73:23-33; 1993.
313. Yamaguchi, F.; Richards, S. J.; Beyreuther, K.; Salbaum, M.; Carlson, G. A.; Dunnett, S. B. Transgenic mice for the amyloid precursor protein 695 isoform have impaired spatial memory. Neuroreport 2: 781-784; 1991.
314. Yamaguchi, H.; Nakazato, H.; Hirai, S.; Shoji, M.; Harigaya, Y. Electron micrograph of diffuse plaques. Initial stage of senile plaque formation in the Alzheimer brain. Am. J. Pathol. 135:593-597; 1989.
315. Yamaguchi, H.; Nakazato, Y.; Shoji, M.; Takatama, M.; Hirai, S. Ultrastructure of diffuse plaques in senile dementia of the Alzheimer type: Comparison with primitive plaques. Acta Neuropathol. 82:13-20; 1992.
316. Yang, F.; Mak, K.; Vinters, H. V.; Frautschy, S. A.; Cole, G. M. Monoclonal antibody to the C-terminus of β-amyloid. Neuroreport 5:2117-2120; 1994.
317. Yankner, B. A.; Dawes, L. R.; Fisher, S.; Villa-Komaroff, L.; Oster-Granite, M. L.; Neve, R. L. Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease. Science 245:417-420; 1989.
318. Yi, S.; Takahashi, K.; Naito, M.; Tashiro, F.; Wakasugi, S.; Maeda, S.; Shimada, K.; Yamamura, K.; Araki, S. Systemic amyloidosis in transgenic mice carrying the human mutant transthyretin (Met30) gene. Am. J. Pathol. 138:403-412; 1991.
319. Yoshikai, S.; Sasaki, H.; Doh-ura, K.; Furuya, H.; Sakaki, Y. Genomic organization of the human amyloid beta-protein precursor gene. Gene 87:257-263; 1990.
320. Zahedi, K.; Gonnerman, W. A.; de Beer, F. C.; de Beer, M. C.; Steel, D. M.; Sipe, J. D.; Whitehead, A. S. Major acute-phase reactant synthesis during chronic inflammation in amyloid-susceptible and -resistant mouse strains. Inflammation 15:1-14; 1991.
321. Zheng, H.; Jiang, M.; Trumbauer, M. E.; Sirinathsinghji, D. J. S.; Hopkins, R.; Smith, D. W.; Heavens, R. P.; Dawson, G. R.; Boyce, S.; Conner, M. W.; Stevens, K. A.; Slunt, H. H.; Sisodia, S. S.; Chen, H. Y.; Van der Ploeg, L. H. T. β-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomoter activity. Cell 81:525-531; 1995.
322. Zhong, Z.; Quon, D.; Higgins, L. S.; Higaki, J.; Cordell, B. Increased amyloid production from aberrant β-amyloid precursor proteins. J. Biol. Chem. 269:12179-12184; 1994.
323. Zola-Morgan, S.; Squire, L. R. Neuroanatomy of memory. Annu. Rev. Neurosci. 16: 547-563; 1993.