Peripheral markers in testing pathophysiological hypotheses and diagnosing Alzheimer's disease

FASEB Journal

Volumn 12, Issue 1, 1998, Pages 17-34

  Gasparini, L ^a   Racchi, M ^a   Binetti, G ^a   Trabucchi, M ^b   Solerte, S B ^c   Alkon, D ^d   Etcheberrigaray, R ^e   Gibson, G ^f   Blass, J ^f   Paoletti, R ^g   Govoni, S ^c,g  

^a IRCCS ISTITUTO CENTRO SAN GIOVANNI DI DIO FATEBENEFRATELLI   (Italy)

^b UNIVERSITY OF ROME TOR VERGATA   (Italy)

^c UNIVERSITY OF PAVIA   (Italy)

^d NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE   (United States)

^e GEORGETOWN UNIVERSITY MEDICAL CENTER   (United States)

^f Medical Research Institute ^*  (United States)

^g UNIVERSITY OF MILAN   (Italy)

Author keywords

CSF; Diagnosis; Peripheral cells; Plasma

Indexed keywords

AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN E; TAU PROTEIN;

AEROBIC METABOLISM; ALZHEIMER DISEASE; ARTICLE; AUTOPSY; CALCIUM HOMEOSTASIS; DEMENTIA; DIAGNOSTIC VALUE; HISTOPATHOLOGY; HUMAN; NEUROENDOCRINOLOGY; PATHOPHYSIOLOGY; PRIORITY JOURNAL; SIGNAL TRANSDUCTION;

EID: 0031985192     PISSN: 08926638     EISSN: None     Source Type: Journal    
DOI: 10.1096/fsb2fasebj.12.1.17     Document Type: Article

References (210)

1. Alzheimer, A. (1907) Uber eine eigenartige Erkrangkung der Himrinde. All. Z. Psychiatr. 64, 146-148
2. Hass, C., and Selkoe, D. J. (1993) Cellular processing of β-amyloid precursor protein and the genesis of amyloid β-peptide. Cell 75, 1039-1042
3. Kang,J., Lemaire, H. G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzaeschik, K. H., Multhaup, G., Beyreuther, K., and Mueller-Hill, B. (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell surface receptor. Nature (London) 325, 733-736
4. Glenner, G. G. (1988) Alzheimer's disease: its problems and genes. Cell 52, 307-308
5. Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., and Binder, L. I. (1986) Abnormal phosphorylation of the microtubule-associated protein tau in Alzheimer cytoskeletal pathology. Proc. Natl. Acad. Sci. USA 83, 4913-4917
6. Mori, H., Kondo, J., and Ihara, Y. (1987) Ubiquitin is a component of paired helical filaments in Alzheimer's disease. Science 235, 1641-1644
7. Dickson, D. W., Crystal, H. A., Mattiace L. A., Masur, D. M., Blau, A., Davies, P., Yen, S.-H., and Aronson M. K. (1992) Identification of normal and pathological aging in prospectively studied nondemented elderly humans. Neurobiol. Aging 13, 1-11
8. Feany, M. B., and Dickson D. W. (1996) Neurodegenerative disorders with extensive tau pathology: a comparative study and review. Ann. Neurol. 40, 139-148
9. Steinberg, D. (1983) Phytanic acid storage disease (Refsum's disease). In The Metabolic Basis of Inherited Disease (Stanbury, J. B., Wyngaarden, J. B., Fredrickson, D. S., Goldstein, J. L., and Brown, M. S., eds) 5th Ed, pp. 731-747, McGraw Hill, New York
10. Stanbury, B., Wyngaarden, J. B., Fredrickson, D. S., Goldstein, J. L., and Brown, M. S. (eds) (1983) The Metabolic Basis of Inherited Disease, 5th Ed, McGraw Hill, New York
11. Balin, A. K., Baker, A. C., Leong, I. C., and Blass, J. P. (1988) Normal replicative lifespan of Alzheimer skin fibroblasts. Neurobiol. Aging 9, 195-198
12. Carmeliet, G., Hauman, R., Dom, R., David, G., Fryns, J.-P., Van Der Berghe, H., and Cassiman, J.-J. (1990) Growth properties and in vitro lifespan of Alzheimer disease and Down syndrome fibroblasts. A blind study. Mech. Ageing Dev. 53, 17-33
13. Carmeliet, G., David, G., and Cassiman, J.-J. (1991) Cellular ageing of Alzheimer's disease and Down syndrome cells in culture. Mutat. Res. 256, 221-231
14. Tesco, G., Vergelli, M., Amaducci, L., and Sorbi, S. (1993) Growth properties of familial Alzheimer skin fibroblasts during in vitro aging. Exp. Gerontol. 28, 51-58
15. Adler, M. J., Coronel, C., Shelton, E., Seegmiller,J. E., and Dewji, N. N. (1991) Increased gene expression of Alzheimer disease β-amyloid precursor protein in senescent cultured fibroblasts. Proc. Natl. Acad. Sci. USA 88, 16-20
16. Tofel-Grehl, B., Blass, J. P., and Gibson, G. E. (1992) Heterogeneity in CDPL to phase out among fibroblasts from different Alzheimer families. Mol. Biol. Cell 35, 1898
17. Blass, J. P., Baker, A. C., Sheu, K.-F. R., Black, R. S., and Smith, A. (1989) Use of cultured skin fibroblasts in studies of Alzheimer' s disease. In Biological Markers of Alzheimer's Disease (Boller, F., Katzman, R., Rascol, A., Signoret, J. L., and Christen, Y., eds) pp. 153-162, Springer-Verlag, New York
18. Sandbrink, R., Hartmann, T., Masters, C. L., and Beyreuther, K. (1996) Genes contributing to Alzheimer's disease. Mol. Psychiat. 1, 27-40
19. Cole, G., Dobkins, K. R., Hansen, L. A., Terry, R. D., and Saitoh, T. (1988) Decreased levels of protein kinase C in Alzheimer brain. Brain Res. 452, 165-174
20. Wang, H.-Y., Pisano, M. R., and Friedman, E. (1994) Attenuated protein kinase C activity and translocation in Alzheimer's disease brain. Neurobiol. Aging 15, 293-298
21. Bosman, G. J., Schurmans-Stekhoven, J. H., Melenhorst, J. J., Van Zuylen, A. J., Bartholomeus, I. G., Van Kalmthout, P. J., and De Grip, W. J. (1992) Are thrombocyte membranes altered in Alzheimer's disease? A morphometric and biochemical study. Neurobiol. Aging 13, 711-716
22. Matsushima, H., Shimohama, S., Tanaka, S., Taniguchi, T., Hagiwara, M., Hidaka, H., and Kimura, J. (1994) Platelet protein kinase C levels in Alzheimer's disease. Neurobiol. Aging 15, 671-674
23. Van Huyn, T., Cole, G., Katzman, R., Huang, K.-P., and Saitoh, T. (1989) Reduced protein kinase C immunoreactivity and altered protein phosphorylation in Alzheimer's disease fibroblasts. Arch. Neurol. 46, 1195-1199
24. Bruel, A., Cherqui, G., Columelli, S., Margelin, D., Roudier, M., Sinet, P.-M., Prieur, M., Perignon, J.-L., and Delabar, J. (1991) Reduced protein kinase C activity in sporadic Alzheimer's disease fibroblasts. Neurosci. Lett, 133, 89-92
25. Govoni, S., Bergamaschi, S., Racchi, M., Battaini, F., Binetti, G., Bianchetti, A., and Trabucchi, M. (1993) Cytosol protein kinase C downregulation in fibroblasts from Alzheimer's disease patients. Neurology 43, 2581-2586
26. Bergamaschi, S., Binetti, G., Govoni, S., Wetsel, W. C., Battaini, F., Trabucchi, M., Bianchetti, A., and Racchi, M. (1995) Defective phorbol ester-stimulated secretion of β-amyloid precursor protein from Alzheimer's disease fibroblasts. Neurosci. Lett. 201, 1-4
27. Racchi, M., Bergamaschi, S., Govoni, S., Wetsel, W. C., Bianchetti, A., Binetti, G., Battaini, F., and Trabucchi, M. (1994) Characterization and distribution of protein kinase C isoforms in human skin fibroblasts. Arch. Biochem. Biophys. 314, 107-111
28. Vestling, M., Adem, M., Lannfelt, L., and Cowburn, R. F. (1995) Protein kinase C levels and activity in cultured skin fibroblasts from affected and non-affected members of the Swedish family with the amyloid precursor protein 670/671 mutation. Soc. Neurosci. Abstr. 21, 774.14
29. Solerte, S. B., Pascale, A., Fortino, I., Battaini, F., Ferrari, E., Fioravanti, M., and Govoni, S. (1996) Cortisol and cytokines modulatory effects on cytosolytic and protein kinase C activities of natural killer in Alzheimer's disease. Neurobiol. Aging 17, 4S, S169
30. Solerte, S. B, Fioravanti, M., Severgnini, M., Cerutti, N., Locatelli, M., Terenzi, F., Cottinelli, M., Pezza, N., and Ferrari, E. (1996) Cortisol, DHEA-sulphate (DEAS) and natural killer (NK) cell functions in the clinical characterization of Alzheimer's disease. J. Endocrinol. Invest. 19, 52
31. Solerte, S. B., Fioravanti, M., Severgnini, S., Locatelli, M., Renzullo, M., Pezza, N., Cerutti, N., and Ferrari, E. (1996) Enhanced cytotoxic response of natural killer cells to interleukin-2 in Alzheimer's disease. Dementia 7, 343-348
32. Huang, H.-M., and Gibson, G. E. (1993) Altered β-adrenergic receptor stimulated cAMP formation in cultured skin fibroblasts from Alzheimer donors. J. Biol. Chem. 268, 14616-14621
33. Huang, H.-M., Lin, T.-A., Sun, G. Y., and Gibson, G. E. (1995) Increased inositol 1,4,5-triphosphate accumulation correlates with an up-regulation of bradykinin receptors in Alzheimer's disease. J. Neurochem. 64, 761-766
34. 3 formation by protein kinase C in human fibroblasts. Life Sci. 59, 1533-1543
35. Selkoe, D. J. (1994) Cell biology of the amyloid β-protein precursor and the mechanism of Alzheimer's disease. Annu. Rev. Cell. Biol. 10, 373-403
36. Sisodia, S. S. (1992) Beta-amyloid precursor protein cleavage by a membrane bound protease. Proc. Natl. Acad. Sci. USA 89, 6075-6079
37. Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus S., Shaffer, L. M., Cai, X.-D., McKay, D. M., Tintner, R., Frangione, B., and Younkin S.,G. (1992) Production of the Alzheimer amyloid β protein by normal proteolytic processing. Science 258, 126-129
38. Buxbaum, J. D., Gandy, S. E., Cicchetti, P., Ehrlich, M. E., Czernik, A. J., Fracasso, R. P., Ramabhadran, T. V., Unterbeck, A. J., and Greengard, P. (1990) Processing of Alzheimer β/A4 amyloid precursor protein: modulation by agents that regulate protein phosphorylation. Proc. Natl. Acad. Sci. USA 87, 6003-6006
39. Gillespie, S. L., Golde, T. E., and Younkin, S. G. (1992) Secretory processing of the Alzheimer amyloid β/A4 precursor is increased by protein phosphorylation. Biochem. Biophys. Res. Commun. 187, 1285-1290
40. Caporaso, G. L., Gandy, S. E., Buxbaum, J. D., Ramabhadran, T. V., and Greengard, P. (1992) Protein phosphorylation regulates secretion of Alzheimer β/A4 amyloid precursor protein. Proc. Natl. Acad. USA 89, 3055-3059
41. Loffler, J., and Huber, G. (1993) Modulation of β-amyloid precursor protein secretion in differentiated and nondifferentiated cells. Biochem. Biophys. Res. Commun. 195, 97-103
42. Hung, A. Y., Haass, C., Nitsch, R. M., Qui, W. Q., Citron, M., Wurtman, R. J., Growdon, J. H., and Selkoe, D. J. (1993) Activation of protein kinase C inhibits cellular production of the amyloid β-protein. J. Biol. Chem. 268, 22959-22962
43. Gabuzda, D., Busciglio, J., and Yankner, B. A. (1993) Inhibition of β-amyloid production by activation of protein kinase C. J. Neurochem. 61, 2326-2329
44. Buxbaum, J. D., Koo, E. H., and Greengard, P. (1993) Protein phosphorylation inhibits production of Alzheimer amyloid β/ A4 peptide. Proc. Natl. Acad. USA 90, 9195-9198
45. Slack, B. E., Nitsch, R. M., Livneh, E., Kunz, G. M., Jr., Breu, J., Eldar, H., and Wurtman, R. J. (1993) Regulation by phorbol esters of amyloid precursor protein release from Swiss 3T3 fibroblasts overexpressing protein kinase Ca. J. Biol. Chem. 268, 21097-21101
46. Querfurth, H. W., Wijsman, E. M., St. George-Hyslop, P. H., and Selkoe, D. J. (1995) βAPP mRNA transcription is increased in cultured fibroblasts from the familial Alzheimer's disease-1 family. Mol Brain Res. 28, 319-337
47. Citron, M., Vigo-Pelfrey, C., Teplow, D. B., Miller, C., Schenk, D., Johnston, J., Winblad, B., Venizelos, N., Lannfelt, L., and Selkoe, D. J. (1994) 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
48. Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., Larson, E., Levy-Lahad, E., Vitanen, M., Peskind E., Poorkaj P., Schellenberg, G., Tanzi, R., Wasco, W., Lannfelt, L., Selkoe, D., and Younkin S. (1996) Secreted amyloid β-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat. Med. 2, 864-870
49. Matsumoto, A., and Fujiwara,Y. (1991) Abnormal and deficient processing of beta-amyloid precursor protein in familial Alzheimer's disease lymphoblastoid cells. Biochem. Biophys. Res. Commun. 175, 361-365
50. Matsumoto, A., and Fujiwara, Y. (1993) Aberrant proteolysis of the beta-amyloid precursor protein in familial Alzheimer's disease lymphoblastoid cells. Eur. J. Biochem. 217, 21-27
51. Govoni, S., Bergamaschi, S., Gasparini, L., Quaglia, C., Racchi, M., Cattaneo, E., Binetti, G., Bianchetti, A., Giovetti, F., Battaini, F., and Trabucchi, M. (1996) Fibroblasts of patients affected by Down's syndrome oversevrete amyloid precursor protein and are hypo responsive to protein kinase C stimulation. Neurology 47, 1-7
52. 2+ homeostasis in Alzheimer's disease. Trends Neurosci. 16, 409-414
53. Mattson, M. P., Cheng, B., Culwell, A. R., Esch, F. S., Lieberburg, I., and Rydell, R. E. (1993) Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of beta-amyloid precursor protein. Neuron 10, 243-254
54. Mattson, M. P., Cheng, B., Davis, D., Bryant, K., Lieberburg, I., and Rydell, R. E. (1992) Beta amyloid peptides destabilize calcium homeostasis and render human cortical neurons vulnerable to excitotoxicity. J. Neurosci. 12, 376-389
55. Mattson, M. P., Tomaselli, K., and Rydell, R. E. (1993) Calcium destabilizing and neurodegenerative effects of aggregated beta-amyloid peptide are attenuated by basic FGF. Brain Res. 621, 34-49
56. Yankner, B. A., Duffy, L. K., and Kirschner, D. A. (1990) Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides. Science 250, 279-282
57. Pike, C., Walencewicz, A., Glabe, C., and Cotman, C. (1991) In vitro aging of beta-amyloid protein causes peptide aggregation and neurotoxicity. Brain Res. 563, 311-314
58. Peterson, C., Gibson, G. E., and Blass, J. P. (1985) Altered calcium uptake in cultured skin fibroblasts from patients with Alzheimer's disease. N. Engl. J. Med. 312, 1063-1064
59. Peterson, C., and Goldman, J. E. (1986) Alterations in calcium content and biochemical processes in cultured skin fibroblasts from aged and Alzheimer donors. Proc. Natl. Acad. Sci. USA 83, 2758-2762
60. Peterson, C., Ratan, R. R., Shelanski, M., and Goldman G. E. (1986) Cytosolic free calcium and cell spreading decrease in fibroblasts from aged and Alzheimer donors. Proc. Natl. Acad. Sci. USA 83, 7999-8001
61. Peterson, C., Ratan, R. R., Shelanski, M., and Goldman, G. E. (1988) Altered response of fibroblasts from aged and Alzheimer donors to drugs that elevate cytosolic free calcium. Neurobiol. Aging 9, 261-266
62. Le Quan Sang, K. H., Mignot, E., Gilbert, J. C., Huguet, R., Aquino, J. P., Regnier, O., and Devynck, M. A. (1993) Platelet cytosolic free calcium concentration is increased in aging and Alzheimer's disease. Biol. Psychiatry 33, 391-393
63. Adunsky, A., Baram, D., Hershkowitz, M., and Mekori, Y. A. (1991) Increased cytosolic free calcium in lymphocytes of Alzheimer patients. J. Neuroimmunol. 33, 167-172
64. Gibson G.E., and Toral-Barza L. (1992) Cytosolic free calcium in lymphoblasts from young, eged and Alzheimer's disease subjects. Mech. Ageing Dev. 63, 1-9
65. Eckert, A., Hartmann, H., and Muller, W. E. (1993) Beta-amyloid protein enhances the mitogen-induced calcium response in circulating human lymphocytes. FEBS Lett. 330, 49-52
66. Eckert, A., Hartmann, H., Forstl, H., and Muller, W. E. (1994) Alterations of intracellular calcium regulation during aging and Alzheimer's disease in nonneuronal cells. Life Sci. 55, 2019-2029
67. Hartmann, H., Eckert, A., and Muller, W. E. (1994) Apolipo-protein E and cholesterol affect neuronal calcium signalling: the possible relationship to beta-amyloid neurotoxicity. Biochem. Biophys. Res. Commun. 200, 1185-1192
68. McCoy, K. R., Mullins, R. D., Newcomb, T. G., Ng, G. M., Pavlinkova, G., Polinsky, R. J., Nee, L. E., and Sisken, J. E. (1993) Serum- and bradykinin-induced calcium transient in familial Alzheimer's fibroblasts. Neurobiol. Aging 14, 447-455
69. Tatebayashi, Y., Takeda, M., Kashiwaggi, Y., Okochi, M., Kurumadani, T., Sekiyama, A., Kanayama, G, Hariguchi, S., and Nishimura, T. (1995) Cell cycle-dependent abnormal calcium response in fibroblasts from patients with familial Alzheimer's disease. Dementia 6, 9-16
70. Huang, H. M., Toral-Barza, L., Thaler, H., Tofel-Grehl, B., and Gibson, G. E. (1991) Inositol phosphates and intracellular calcium after bradykinin stimulation in fibroblasts from young, normal aged and Alzheimer donors. Neurobiol. Aging 12, 469-473
71. i transients are similar in fibroblasts from normal and Alzheimer's donors. Neurobiol. Aging 13, 33-38
72. 2+) in mononuclear blood cells from demented patients and healthy controls. Eur. Arch. Psychiatry Clin Neurosci. 243, 224-228
73. 2+ mobilization is altered in fibroblasts from patients with Alzheimer disease. Proc. Natl. Acad. Sci. USA 91, 534-538
74. Gibson, G. E., Zhang, H., Toral-Barza, L., Szolosi, S., and Tofel-Grehl, B. (1996) Calcium stores in cultured fibroblasts and their changes with Alzheimer's disease. Biochim Biophys Acta 1316, 71-77
75. Kumar, U., Dunlop, D. M., and Richardson, J.S. (1994) Mitochondria from Alzheimer's fibroblasts show a decreased uptake of calcium and increased sensitivity to free radicals. Life Sci. 54, 1855-1860
76. Etcheberrigaray, R., Ito, E., Oka, K., Tofel-Grehl, B., Gibson, G. E., and Alkon, D. L. (1993) Potassium channel dysfunction in fibroblasts identifies patients with Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 8209-8213
77. Matsuyama, S. S.,Yamagnchi, D. T., Vegara, J., and Jarvik, L. F. (1995) Tetraethylammonium-induced calcium concentration changes in skin fibroblasts from patients with Alzheimer's disease. Dementia 6, 241-244
78. Gibson, G. E., Martins, R., Blass, J., and Gandy, S. (1996) Altered oxydation and signal transduction systems in fibroblasts from Alzheimer's patients. Life Sci. 59, 477-490
79. Sims, N. R., Finegan, J. M., and Blass, J. P. (1987) Altered metabolic properties of cultured skin fibroblasts in Alzheimer's disease. Ann. Neurol. 21, 451-456
80. Sorbi, S., Piacentini, S., Latorraca, S., Piersanti P., and Amaducci, L. (1995) Alterations in metabolic properties in fibroblasts in Alzheimer's disease. Alzheimers Dis. Assoc. Disord. 9, 73-77
81. Gibson, G. E., Sheu, K.-F. R., Blass, J. P., Baker, A., Carlson, K. C., Harding, B., and Perrino, P. (1988) Reduced activity of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer's disease. Arch. Neurol. 45, 836-840
82. Sheu, K. R., Cooper, A. J. L., Koike, K., Koike, M., Lindsay, G., and Blass, J. P. (1994) Abnormality of the α-ketoglutarate dehydrogenase complex in fibroblasts from Alzheimer's disease. Ann. Neurol. 35, 312-318
83. Blass J. P., Kwan-Fu, R. S., Piacentini, S., and Sorbi, S. (1997) Inherent abnormalities in oxidative metabolism in AD: interaction with vascular abnormalities. In press
84. Cooper A. L., Sheu K. F., and Blass J. P. (1996) Normal glutamate metabolism inAlzheimer's disease fibroblasts deficient in alpha-ketoglutarate dehydrogenase complex activity. Dev. Neurosci. 18, 499-504, 1996
85. Parker, W. D., Filley, C. M., and Parks J. K. (1990) Cytochrome c oxidase deficiency in Alzheimer's disease. Neurology 40, 1302-1303
86. Davis, R. E., Miller, S., Herrnstadt, C., Ghosh S. S., Fahy, E., Shinobu, L. A., Galasko, D., Thal, L. J., Beal, M. F., Howell, N., Parker, D. W. (1997) Mutations in mitochondrial cytochrome c oxidase genes segregate with late onset Alzheimer's disease (1997) Proc. Natl. Acad. Sci. USA 94, 4526-4531
87. Hirashima, N., Etcheberrigaray, R., Bergamaschi, S., Racchi, M., Battaini, F., Binetti, G., Govoni, S., and Alkon, D. L. (1996) Calcium responses in human fibroblasts: a diagnostic molecular profile for Alzheimer's disease. Neurobiol Aging 17, 549-555
88. Van Nostrand, W. E., Schmaier, A. H., and Wagner, S. L. (1992) Potential role of protease nexin-2/amyloid beta-protein precursor as cerebral anticoagulant. Ann. N.Y. Acad. Sci. 674, 243-252
89. Van Nostrand, W. E., Schmaier, A. H., Farrow, J. S., and Cunningham, D. D. (1990) Protease nexin-II (amyloid beta-protein precursor): a platelet alpha-granule protein. Science 248, 745-748
90. Van Nostrand, W. E., Wagner, S. L., Suzuki, M., Choi, B. H., Farrow, J. S., Geddes, J. W., Cotman, C. W., and Cunningham, D. D. (1989) Protease nexin-II, a potent antichymotrypsin, shows identity to amyloid beta-protein precursor. Nature (London) 341, 546-549
91. Li, Q. X., Evin, G., Small, D. H., Multhaup, G., Beyreuther, K., and Masters, C. L. (1995) Proteolytic processing of Alzheimer's disease beta A4 amyloid precursor protein in human platelets. J. Biol. Chem. 270, 14140-14147
92. Li, Q. X. Berndt, M. C., Bush, A. I., Rumble, B., Mackenzie, I., Friedhuber, A., Beyreuther, K., and Masters, C. L. (1994) Membrane-associated forms of the beta A4 amyloid protein precursor of Alzheimer's disease in human platelet and brain: surface expression on the activated human platelet. Blood 84, 133-142
93. Gardella, J. E., Gorgone, G. A., Munoz, P. C., Ghiso, J., Frangione, B., and Gorevic, P. D. (1992) Beta protein precursor expression in human platelets and a megakaryocyte cell line. Possible implications for the origin of cerebral amyloidosis in Alzheimer's disease. Lab. Invest. 67, 303-313
94. Di Luca, M., Pastorino, L., Cattabeni, F., Zanardi, R., Racagni, G., Smeraldi, E., and Perez, J. (1996) Abnormal pattern of platelet APP isoforms in Alzheimer's disease and Down syndrome. Arch. Neurol. 53, 1162-1166
95. Henriksson, T., Barbour, R. M., Braa, S., Ward, P., Fritz, L. C., Johnson-Wood, K., Chung, H. D., Burke, W., Reinikainen, K. J., Riekkinen, P., and Schenk, D. B. (1991) Analysis and quantitation of the β-amyloid precursor protein in the cerebro- spinal fluid of Alzheimer's disease patients with a monoclonal antibody-based immunoassay. J. Neurochem. 56, 1037-1042
96. Prior, R., Monning, U., Schreiter-Gasser, U., Weidemann, Blennow, K, Gottfries, C. G., Masters, C. L., and Beyreuther, K. (1991) Quantitative changes in the amyloid βA4 precursor protein in Alzheimer cerebrospinal fluid. Neurosci. Lett. 124, 69-73
97. Farlow, M., Ghetti, B., Benson, M. D., Farrow, J. S., Van Nostrand, W. E., and Wagner, S. L. (1992) Low cerebrospinal-fluid concentrations of soluble amyloid β-protein precursor in hereditary Alzheimer's disease. Lancet 340, 453-454
98. Lannfelt, L., Basun, B., Wahlund, L.-O., Rowe, B. A., Wagner, S. (1995) decreased cerebrospinal fluid alpha-secretase cleaved amyloid precursor protein as diagnostic marker for Alzheimer's disease. Nature Med. 1, 829-832
99. Palmert, M. R., Usiak, M., Mayeux, R., Raskind, M., Tuortel-Iotte, W. W., and Younkin, S. G. (1990) Soluble derivatives of the β amyloid protein precursor in cerebrospinal fluid: alterations in normal aging and in Alzheimer's disease. Neurology 40, 1028-1034
100. Van Nostrand, W. E., Wagner, S. L., Shankle, W. R., Farrow, J. S., Dick, M., Rozemuller, J. M. Kuiper, M. A., Wolters, E. C., Zimmerman, J., Cotman, C. W., and Cunningham, D. D. (1992) Decreased levels of soluble amyloid β-protein precursor in cerebrospinal fluid of live Alzheimer disease patients. Proc. Natl. Acad. Sci USA 89,2551-2555
101. Almkvist, O., Basun, H., Wagner, S. L., Rowe, B. A., Wahlund, L.-O., and Lannfelt, L. (1997) Cerebrospinal fluid levels of alpha secretase cleaved soluble amyloid precursor protein mirror cognition in Swedish family with Alzheimer's disease and a gene mutation. Arch. Neurol. 54, 641-647
102. Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schlossmacher, Whaley, J., Swindlehurst, C., McCormack, R., Wolfert, R., Selkoe, D. J., Lieberburg, I., and Schenk, D. (1992) Isolation and quantification of soluble Alzheimer's β-peptide from biological fluid. Nature (London) 359, 325-327
103. Nakamura, T., Shoji, M., Harigaya, Y., Watanabe, M., Hosoda, K., Cheung, T. T., Shaffer, L. M., Golde, T. E., Younkin, L. H., Younkin, S. G., and Shunsaku, H. (1994) Amyloid β-protein levels in cerebrospinal fluid are elevated in early onset Alzheimer's disease. Ann. Neurol. 36, 903-911
104. Nitsch, R. M., Rebeck, G. W., Deng, M., Richardson, U. I., Tennis, M., Schenk, D. B., Vigo-Pelfrey, C., Lieberburg, I., Wurtman, R. J., Hyman, B. T., and Growdon, J. H. (1995) Cerebrospinal fluid levels of amyloid β-protein in Alzheimer's disease: inverse correlation with severity of dementia and effect of apolipoprotein E genotype. Ann. Neurol. 37, 512-518
105. Lannfelt, L., Basun, H., Vigo-Pelfrey, C., Wahlund, L.O., Winblad, B., Lieberburg, I., and Schenk, D. (1995) Amyloid β-peptide in cerebrospinal fluid in individuals with the Swedish Alzheimer amyloid precursor protein mutation. Neurosci. Lett. 199, 203-206
106. Tabaton, M., Nunzi, M. G., Xue, R., Usiak, M., Autilio-Gambetti, L., and Gambetti, P. (1994) Soluble amyloid β-protein is a marker of Alzheimer amyloid in brain but not in cerebrospinal fluid. Biochem. Biophys. Res. Commun. 200, 1598-603
107. Southwick, P. C., Yamagata, S. K., Echols, C. L., Jr., Higson, G. J., Neynaber, S. A., Parson, R. E., and Munroe, W. A. (1996) Assessment of amyloid β protein in cerebrospinal fluid as an aid in the diagnosis of Alzheimer's disease. J. Neurochem. 66, 259-265
108. Van Gool, W. A., Kuiper, M. A., Walstra, G. J. M., Wolters, E. C., and Bolhuis, P. A. (1995) Concentrations of amyloid β protein in cerebrospinal fluid of patients with Alzheimer's disease. Ann. Neurol. 37, 277-279
109. Motter, R., Vigo-Pelfrey, C., Kholodenko, D., Barbour, R., Johnson-Wood, K., Galasko, D., Chang, L., Miller, B., Clark, C., Green, R., Olson, D., Southwick, P., Wolfert, R., Munroe, B., Lieberburg, I., Seubert, P., and Schenk, D. (1995) Reduction of β-amyloid peptide 42 in the cerebrospinal fluid of patients with Alzheimer's disease. Ann. Neurol. 38, 643-648
110. Schenk, D., Motter, R., Kholodenko, D., Lieberburg, I., and Seubert, P. (1996) Aβ 42 and tau as markers of Alzheimer's disease. Neurobiol. Aging 17, S1
111. Ida, N., Hartmann, T., Pantel,J., Schroder,J., Zerfass, R., Forstl, H., Sandbrink, R., Masters, C. L., and Beyreuther, K. (1996) Analysis of heterogeneous βA4 peptides in human cerebrospi- nal fluid and blood by a newly developed sensitive western blot assay. J. Biol. Chem. 271, 22908-22914
112. Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., and Ihara, Y. (1994) Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific monoclonals: evidence that an initially deposited species is Aβ42(43). Neuron 13, 45-52
113. Roher, A., Lowenson, J., Clarke, S., Wolkow, C., Wang, R., Cotter, R. J, Reardon, I. M, Zurcher-Neely, H. A, Heinrikson, R. L., Ball, M. J., et al. (1993) 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
114. Song, X. H., Suzuki, N., Bird, T., Peskind, E., Schellenberg, G., and Younkin, S. G. (1995) Plasma amyloid β protein (Aβ) ending at Aβ42(43) is increased in carriers of familial AD (FAD) linked to chromosome 14. Soc. Neurosci. Abstr. 21, 1501
115. Jensen, M., Song, X. H. Suzuki, N., Lannfelt, L., and Younkin, S. G. (1995) The βAPP670/671 Alzheimer mutation (Swedish) increases plasma amyloid β protein concentration. Soc. Neurosci. Abstr. 21, 1501
116. Younkin, L. H., Eckman, C. B., Yager, D., Graff-Rafford, N., and Younkin, S. G. (1996) Analysis of plasma Aβ concentration in sporadic AD patients and non-demented subjects of all ages. Neurobiol. Aging 17, S167
117. Kosaka, T., Imagawa, M., Seki, K., Arai, H., Sasaki, H., Tsuji, S., Asami-Odaka, A., Fukushima, T., Ima, K., and Iwatsubo, T. (1997) The βAPP717 Alzheimer mutation increases the percentage of plasma amyloid-β protein ending at Aβ42(43). Neurology 48, 741-745
118. Tato, R. E., Frank, A., and Hernanz, A. (1995) Tau protein concentrations in cerebrospinal fluid of patients with dementia of the Alzheimer type. J. Neurol. Neurosurg. Psychiat. 59, 280-283
119. Vigo-Pelfrey, C., Seubert, P., Barbour, R., Blomquist, C., Lee, M., Lee, D., Coria, F., Chang, L., Miller, B., Lieberburg, I., et al. Elevation of microtubule-associated protein tau in the cerebrospinal fluid of patients with Alzheimer's disease. (1995) Neurology 45, 788-793
120. Munroe, W. A., Southwick, P. C., Chang, L., Scharre, D. W., Echols, C. L., Jr., and Fu, P. C. (1995) Tau protein in cerebrospinal fluid as an aid in the diagnosis of Alzheimer's disease. Ann. Clin. Lab. Sci. 25, 207-217
121. Vandermeeren, M., Mrecken, M., Vanmechelen, E., Six, J., Van de Voorde, A., Martin, J. J., and Cras, P. (1993) Detection of τ proteins in normal and Alzheimer's disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunoassorbent assay. J. Neurochem. 61, 1828-1834
122. Jensen, M., Basun, H., and Lannfelt, L. (1995) Increased cerebrospinal fluid tau in patients with Alzheimer's disease. Neurosci. Lett. 186, 189-191
123. Arai, H., Terajima, M., Miura, M., Higuchi, S., Muramatsu, T., Machida, N., Seiki, H., Takase, S., Clark, C. M., Lee, V. M.-Y., Trojanowski, J. Q., and Sasaki, H. (1995) Tau in cerebrospinal fluid: a potential diagnostic marker in Alzheimer's disease. Ann. Neurol. 38, 649-652
124. Galasko, D., Clark, C., Chang, L., Miller, B., Green, R. C., Motter, R., and Seubert P. (1997) Assessment of cerebrospinal fluid levels of tau in mildly demented patients with Alzheimer's disease. Neurology 48, 632-635
125. Blomberg, M., Jensen, M., Basun, H., Lannfelt, L., and Wahlund, L.-O. (1996) Increased of CSF tau levels in most Alzheimer patients during 15 months follow-up. Neurobiol. Aging 17, S167
126. Johnson, G. V. W., Seubert, P., Cox, T. M., Motter, R., Brown, J. P., and Galasko, D. (1997) The tau protein in human cerebrospinal fluid in alzheimers disease consists of proteolytically derived fragments. J. Neurochem. 68, 430-433
127. Blennow, K., Wallin, A., Agren, H., Spenger, C., Siegfried, J., and Vanmechelen, E. (1995) Tau protein in cerebrospinal fluid. A biochemical marker for axonal degeneration in Alzheimer's disease? Mol. Chem. Neuropathol. 26, 231-245
128. Kennard, M. L., Feldman, H., Yamada, T., and Jefferies, W. A. (1996) Serum levels of the iron binding protein p97 are elevated in Alzheimer's disease. Nat. Med. 2, 1230-1235
129. Ball, M. J. (1978) Topographic distribution of neurofibrillary tangles and granulovacuolar degeneration in hippocampal cortex of aging and demented patients. A quantitative study. Acta Neuropathol. 42, 73-80
130. Coleman, P. D., and Flood, D. G. (1987) Neuron numbers and dendritic extent in normal aging and Alzheimer's disease. Neurobiol. Aging 8, 521-545
131. Sapolski, R. M., Zolari-Morgan, S., and Squire, L. R. (1991) Inhibition of glucocorticoid secretion by the hippocampal formation in the primate. J. Neurosci. 11, 3695-3704
132. Dunn, I. D., and Orr, S. E. (1984) Differential plasma corticosterone responses to hippocampal stimulation. Brain Res. 54, 1-8
133. Lorens, S. A., Hata, N., Handa, R. J., Van de Kar, L. D., Guschwanb, M., Goral, J., Lee, J. M., Hamiltor, M. E., Bethea, C. L., and Clancy, J. (1990) Neurochemical, endocrine and immunological response to stress in young and old Fisher 344 male rats. Neurobiol. Aging 11, 139-150
134. Reul, J. M., Tonnaer, J. A. D. M., and de Kloet, E. R. (1988) Neurotropic ACTH analog promotes plasticity of type I corticosteroid receptors in brain of senescent rats. Neurobiol. Aging 9, 253-260
135. Reul, J. M. H. M., Rothuizen, J., and de Kloet, E. R. (1991) Age-related changes in the dog hypothalamic-pituitary-adrenocortical system: neuroendocrine activity and corticosteroid receptors. J. Steroid Biochem. Mol. Biol. 40, 63-69
136. Heuser, I. J., Gotthardt, U., Schweiger, U., Schmider, J., Lammers, C. H., Dealing, M., and Holsboer, F. (1994) Age-associated changes of pituitary-adrenocortical hormone regulation in humans: importance of gender. Neurobiol. Aging 15, 227-231
137. Hatzinger, M., Z'Brun, A., Hemmeter, U., Seifritz, E, Baumann, F., Holsboer-trachsler, E., and Heuser, I. J. (1995) Hypothalamic-pituitary-adrenal system function in patients with Alzheimer's disease. Neurobiol. Aging 16, 205-209
138. May, C., Rapoport, S. I., Tomai, T. P., Chrousos, G. P., and Gold, P. W. (1987) Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH) and corticotropin (ACTH) are reduced in patients with Alzheimer's disease. Neurology 37, 535-538
139. Facchinetti, F., Nappi, G., Petraglia, F., Martignoni, E., Sinforiani, E., and Genazzani, A. R. (1984) Central ACTH deficit in degenerative and vascular dementia. Life Sci. 35, 1691-1697
140. Suemaru, S., Suemaru, K., Hashimoto, K., Ogasa, T., Hirasawa, R., Makino, S., and Kageyama, J. (1993) Cerebrospinal fluid corticotropin-releasing hormone and ACTH, and peripherally circulating choline-containing phospholipid in senile dementia. Life Sci. 53, 697-706
141. Suemaru, S., Hashimoto, K., Ogasa, T., Hirasawa, R. V., Makino, S., Ota, Z., Kageyama, J., and Suemaru, K. (1991) Cerebrospinal fluid and plasma corticotropin-releasing hormone in senile dementia. Life Sci. 48, 1871-1879
142. De Souza, E. B., Whitehouse, P. J., Kuhar, M. J., Price, D. L. V., and Vale, W. W. (1986) Reciprocal changes in corticotropin-releasing factor (CRF)-Iike immunoreactivity and CRF receptors in cerebral cortex of Alzheimer's disease. Nature (London) 319, 593-595
143. Whitehouse, P. J, Vale, W. W., Zweig, R. M. V., Singer, H. S, Mayeux, R., Kuhar, M. J., Price, D. L., and De Souza, E. B. (1987) Reductions in corticotropin releasing factor-like immunoreactivity in cerebral cortex in Alzheimer's disease, Parkinson's disease, and progressive supranuclear palsy. Neurology 37, 905-909
144. Bissette, G., Reynolds, G. P., Kilts, C. D., Widerlov, E., and Nemeroff, C. B. (1985) Corticotropin-releasing factor-like immunoreactivity in senile dementia of the Alzheimer type. J. Am. Med. Assoc. 254, 3067-3069
145. De Souza, E. B., Whitehouse, P. J., Price, D. L., and Vale, W. W. (1987) Abnormalities in corticotropin-releasing hormone (CRH) in Alzheimer's disease and other human disorders. Ann. N.Y. Acad. Sci. 512, 236-247
146. Lesch, K. P., Ihl, R., Frolich, L., Rupprecht, R., Muller, U., Schulte, H.M., and Maurer, K. (1990) Endocrine responses to growth hormone releasing hormone and corticotropin releasing hormone in early-onset Alzheimer's disease. Psychiatry Res. 33, 107-112
147. Ghiso, E., Nicolosi, M., Arvat, E., Marcone, A., Danelon, F., Mucci, M., Franceschi, M., Smirne, S., and Camanni, F. (1993) Growth hormone secretion in Alzheimer's disease: studies with growth hormone releasing hormone alone and combined with pyridostigmine or arginine. Dementia 4, 315-320
148. Muriaido, G., Zerbi, F., Filippi, U., Tosca, P., Fonzi, F., Di Paolo, E., Costelli, F., Porro, S., Polleri, A., and Savoldi, F. (1990) Cholinergic modulation of growth hormone-releasing hormone effects on growth hormone secretion in dementia. Neuropsychobiology 24, 129-314
149. Gomez, J. M., Aguilar, M., Navarro, M. A., Ortola, J., and Soler, J. (1994) Secretion of growth hormone and thyroid-stimulating hormone in patients with dementia. Clin. Invest. 72, 489-493
150. Edvinsson, L., Minthon, L., Ekman, R., and Gustafson, L. (1993) Neuropeptides in cerebrospinal fluid of patients with Alzheimer's disease and dementia with frontotemporal lobe degeneration. Dementia 4, 167-171
151. Albert, M., Jenike, M., Nixon, R., and Nobel, K. (1993) Thyrotropin response to thyrotropin-releasing hormone in patients with dementia of the Alzheimer type. Biol. Psychiatry 33, 267-271
152. Dysken, M. W., Falk, A., Pew, B., Kuskowski, M., and Krahn, D. D. (1990) Gender differences in TRH-stimulated TSH and prolactin in primary degenerative dementia and elderly controls. Biol. Psychiatry 28, 144-150
153. Bierer, L. M., Haroutunian, V., Gabriel, S., Knott, P. J., Carlin, L. S., Purohit, D. P., Perl, D. P., Schmeidler, J., Kanof, P., and Davis, K. L. (1995) Neurochemical correlates of dementia severity in Alzheimer's disease: relative importance of the cholinergic deficits. J. Neurochem. 64, 749-760
154. Beal, M. F. (1990) Somatostatin in neurodegenerative illnesses. Metabolism 39, 116-119
155. Leake, A., and Ferrier, I. N. (1993) Alterations in neuropeptides in aging and disease. Pathophysiology and potential for clinical intervention. Drugs Aging 3, 408-27
156. Reinikainen, K. J., Koponen, H., Jolkkonen, J., and Riekkinen, P. J. (1990) Decreased somatostatin-like immunoreactivity in the cerebrospinal fluid of chronic schizophrenic patients with cognitive impairment. Psychiatry Res. 33, 307-312
157. Wallin, A., Carlsson, A. V., Ekman, R., Gottfries, C. G., Karlsson, I., Svennerholm, L., and Widerlov, E. (1991) Hypothalamic monoamines and neuropeptides in dementia. Eur. Neuropsychopharmacol, 1, 165-168
158. Molchan, S. E., Hill, J. L., Martinez, R. A., Lawlor, B. A., Mellow, A. M., Rubinow, D. R., Bissette, G. V., Nemeroff, C. B., and Sunderland, T. (1993) CSF somatostatin in Alzheimer's disease and major depression relationship to hypothalamic-pituitary-adrenal axis and clinical measures. Psychoneuroendocrinology 18, 509-519
159. Yasuda, M., Minamitani, N., and Maeda, K. (1993) Peptide histidine methionine in cerebrospinal fluid of patients with senile dementia of the Alzheimer type. Jpn. J. Psychiatry Neurol. 47, 85-90
160. Hartikainen, P., Reinikainen, K.J., Soininen, H., Sirvio,J., Soikkeli, R., and Riekkinen, P. J. (1992) Neurochemical markers in the cerebrospinal fluid of patients with Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and normal controls. J. Neurol. Trans. Parkinson Dis. Dement. Sect. 4, 53-68
161. Wikkelso, C., Ekman, R., Westergren, I., and Johansson, B. (1991) Neuropeptides in cerebrospinal fluid in normal pressure hydrocephalus and dementia. Eur. Neurol. 31, 88-93
162. Minthon, L., Edvinsson, L., Ekman, R., and Gustafson, L. (1990) Neuropeptide levels in Alzheimer's disease and dementia with frontotemporal degeneration. J. Neurol. Trans. Suppl. 30, 57-67
163. Reinikainen, K. J., Soininen, H., and Riekkinen, P. J. (1990) (A) Neurotrasmitter changes in Alzheimer's disease: implications to diagnostics and therapy. J. Neurosci. Res. 27, 576-586
164. Koponen, H., Reinikainen, K. J., Jolkkonen, J. Y., and Riekkinen, P. J. (1990) Somatostatin-like immunoreactivity in the CSF of patients with dementia associated with alcoholism. Acta Neurol. Scand. 82, 289-291
165. Banki, C. M., Karmacsi, L., Bissette, G., and Nemeroff, C. B. (1992) Cerebrospinal fluid neuropeptides in mood disorder and dementia. J. Affective Disord. 25, 39-45
166. Strittmatter, M. M., and Cramer, H. (1992) Parkinson's disease and dementia: clinical and neurochemical correlations. Neuroreport 3, 413-416
167. Molins, A., Catalan, R., Sahuquillo,J., Castellanos,J.M., Codina, A., and Galard, R. (1991) Somatostatin cerebrospinal fluid levels in dementia. J. Neurol. 238, 168-170
168. Leake, A., Perry, E. K., Perry, R. H., Jabeen, S., Fairbairn, A. F., McKeith, I. G., and Ferrier, I. N. (1991) Neocortical concentrations of neuropeptides in senile dementia of the Alzheimer and Lewy body type: comparison with Parkinson's disease and severity correlations. Biol. Psychiatry 29, 357-364
169. Tang, M. X., Jacobs, D., Stern Y., Marder, K., Schofield, P., Gurland, P., andrews, H., and Mayeux, R. (1996) Effect of estrogen during menopause on risk and age at onset of Alzheimer's disease. Lancet 348, 429-432
170. Henderson, V. W., Paganini-Hill, A., Emanuel, C. D., Dunn, M. E., and Buckwater, J. G. (1994) Estrogen replacement therapy in older women: comparison between Alzheimer's disease cases and non-demented controls. Arch. Neurol. 51, 896-899
171. Eikelenboom, P., and Veerhuis, R. (1996) The role of complement and activated microglia in the pathogenesis of Alzheimer's disease. Neurobiol. Aging 17, 673-680
172. Roger, J., Webster, S., Fue, L.-F., Brachova, L., Civin, W. H., Emmerling, M., Shivers, B., Walker, D., and McGeer, P. (1996) Inflammation and Alzheimer's disease. Neurobiol. Aging 17, 681-686
173. Kalaria, R. N., Harshbarger-Kelly, M., Coher, D. L., and Premkumar, D. R. D. (1996) Molecular aspects of inflammatory and immume responses in Alzheimer's disease. Neurobiol. Aging 17, 687-694
174. Weisgraber, K. H., Roses, A. D., and Strittmatter, W. J. (1994) The role of apolipoprotein E in the nervous system. Curr. Opin. Lipidol. 5, 110-116
175. Pitas, R. E., Boyles, J. K., Lee, S. H., Foss, D., and Mahley, R. W. (1987)Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins. Biochem. Biophys. Acta 917, 148-161
176. Poirier, J. (1994) Apolipoprotein E in animal models of CNS injury and in Alzheimer's disease. Trends Neurosci. 17, 525-530
177. Ignatius, M. J., Gebicke-Harter, P. J., Skene, J. H. P., Schilling, J. W., Weisgraber, K. H., Mahley, R. W., and Shooter, E. M. (1986) Expression of apolipoprotein E during nerve degeneration and regeneration. Proc. Natl. Acad. Sci. USA 83, 1125-1129
178. Snipes, G. J. V., McGuire, C. B., Norden, J. J., and Freeman, J. A. (1986) Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cells. Proc. Natl. Acad. Sci. USA 83, 1130-1134
179. Namba,Y., Tomonaga, M., Kawasaki, H., Otomo, E., and Ikeda, K. (1991) Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jacob disease. Brain Res. 41, 163-166
180. Strittmatter, W. J. Saunders, A. M., Schmechel, D., Pericak-Vance, M., Enghild, J., Salvesen, G. S., and Roses, A. D. (1993) Apolipoprotein E-high avidity binding to β-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 1977-1981
181. 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., Alberts, M. J., Hulette, C., Crain, B., Goldgaber, D., and Roses, A. D. (1993) Association of apolipoprotein E allele ∈4 with late-onset familial and sporadic Alzheimer's disease. Neurology 43, 1467-1472
182. Peacock, M. L., and Fink,J. K. (1994) ApoE ∈4 allelic association with Alzheimer's disease: independent confirmation using deneturing gradient gel electrophoresis. Neurology 44, 339-341
183. Ueki, A., Kawano, M., Namba, Y., Kawakami, M., and Ikeda, K. (1993) A high frequency of apolipoprotein E4 isoprotein in Japanese patients with late-onset nonfamilial Alzheimer's disease. Neurosci. Lett. 163, 166-168
184. Kuusisto, J., Koivisto, K., Kervinen, K., Mykkanen, L., Helkala, E. L., Vanhanen, M., Hanninan, T., Pyorala, K., Kesaniemi, Y. A., Riekkinen, P., and Laakso, M. (1994) Association of apolipoprotein E phenotypes with late onset Alzheimer's disease: population based study. Br. Med. J. 309, 636-638
185. Heinonen, O., Lehtovirta, M., Soininen, H., Helisalmi, S, Mannermaa, A., Sorvari, H., Kosunen, O., Paljarvi, L., Ryynanen, M., and Riekkinen, P. J. (1995) Alzheimer pathology of patients carrying apolipoprotein E epsilon 4 allele. Neurobiol. Aging 16, 505-513
186. Frisoni, G. B., Calabresi, L., Geroldi, C., Bianchetti, A., D'Acquarica, A. L., Govoni, S., Sirtori, C. R., Trabucchi, M., and Franceschini, G. (1994) Apolipoprotein E ∈4 allele in Alzheimer's disease and vascular dementia. Dementia 5, 240-242
187. Sorbi, S., Nacmias, B., Forleo, P., Latorraca, S., Gobbini, I., Bracco, L., Piacentini, S., and Amaducci, L. (1994) ApoE allele frequencies in Italian sporadic and familial Alzheimer's disease. Neurosci.Lett. 177, 100-102
188. Dai, X. Y., Nanko, S., Hattori, M., Fukuda, R., Nagata, K., Isse, K., Ueki, A., and Kazamatsuri, H. (1994) Association of apolipoprotein E4 with sporadic Alzheimer's disease is more pronounced in early onset type. Neurosci. Lett. 175, 74-76
189. Van Duijn, G. M., de Knijff, P., Cruts, M., Wehnert, A., Havekes, L. M., Hofman, A., and Van Broeckhoven, C. (1994) Apolipoprotein E4 allele in a population-based study of early-onset Alzheimer's disease. Nat. Genet. 7, 74-78
190. Schmechel, D. E., Saunders, A. M., Strittmatter, W. J., Crain, B.J., Hulette, C. M., Joo, S. H., Pericak-Vance, M. A., Goldgaber, D., and Roses, A. D. (1993) Increased amyloid β-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 9649-9653
191. Tsal, M. S., Tangalos, E. G., Petersen, R. C., Smith, G. E., Schald, D. J., Kokmen, E., Ivnik, R. J., and Thibodeau, S. N. (1994) Apolipoprotein E: risk factor for Alzheimer disease. Am. J. Hum. Genet. 54, 643-649
192. Saunders, A. M., Hulette, C., Welsh-Bohmer, K. A., Schmechel, D. E., Crain, B., Burke, J. R., Alberts, M. J., Strittmatter, W. J., Breitner, J. C. S., Rosenberg, C., Scott, S. V., Gaskell, P. C., Jr., Pericak-Vance, M. A., and Roses, A. D. (1996) Specificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease. Lancet 348, 90-93
193. Frisoni, G. B., Geroldi, C., Bianchetti, A., Binetti, G., and Trabucchi, M. (1996) The gain of apolipoprotein E genotyping to separate Alzheimer's disease from normal individuals: relevance to community studies. Dementia 7, 336-342
194. Frisoni, G. B., Bianchetti, A., Govoni, S., and Trabucchi, M. (1996) Diagnostic usefulness of apolipoprotein E ∈4 in the diagnosis of the dementia (letter). J. Neurol. Neurosurg. Psychiat. 60, 699-700
195. Amouyel, P., Vidal, O., Launay, J. M., and Laplanche, J. L. (1994) The apolipoprotein E alleles as major susceptibility factors for Creutzfeldt-Jacob disease. Lancet 344, 1315-1318
196. St. Clair, D., Norrman, J., Perry, R., Yates, C., Wilcock, G., and Brookes, A. (1994) Apolipoprotein E ∈4 allele frequency in patients with Lewy body dementia, Alzheimer's disease and age-matched controls. Neurosci. Lett. 176, 45-46
197. Van Gool, W. A., Evenhuis, H. M., and van Duijn, C. M., on behalf of the Dutch Study Group on Down's syndrome and Ageing. (1995) A case-control study of apolipoprotein E genotypes in Alzheimer's disease associated with Down's syndrome. Ann. Neurol. 38, 225-230
198. Mann, D. M. A., Pickering-Brown, S. M., Siddons, M. A., Iwatsubo, T., Ihara, Y., Asami-Okada, A., and Suzuki, N. (1995) The extent of amyloid deposition in brain in patients with Down's syndrome does not depend upon the apolipoprotein E genotype. Neurosci Lett. 196, 105-108
199. Poirier, J., Delisle, M.-C., Quirion, R., Aubert, I., Farlow, M., Lahiri, D., Hui, S., Bertrand, P., Nalbantoglu, J., Gilfix, B. M., and Gauthier, S. (1995) Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer disease. Proc. Natl. Acad. Sci. USA 92, 12260-12264
200. Roses, A. D, Strittmatter, W. J., and Pericak-Vance, M. A. (1994) Clinical application of apolipoprotein E genotyping to Alzheimer's disease. Lancet 343, 1564-1565
201. Frisoni, G. B., Geroldi, C., Bianchetti, A., Calabresi, L., Franceschini, G., and Trabucchi, M. (1995) Gene dose of the ∈4 allele of apolipoprotein E and disease progression in sporadic late-onset Alzhiemer's disease. Ann. Neurol. 37, 596-604
202. Blennow, K., Hesse, C., and Fredman, P. (1994) Cerebrospinal fluid apolipoprotein E is reduced in Alzheimer's disease. Neuroreport 5, 2534-2536
203. Lehtimaki, T., Pirttila, T., Mehta, P. D., Wisniewski, H. M., Frey, H., and Nikkari, T. (1995) Apolipoprotein E (apoE) polymorphism and its influence on ApoE concentrations in the cerebrospinal fluid in Finnish patients with Alzheimer's disease. Human Genet. 95, 39-42
204. Landen, M., Hesse, C., Fredman, P., Regland, B., Wallin, A., and Blennow, K. (1996) Apolipoprotein E in cerebrospinal fluid from patients with Alzheimer's disease and other forms of dementia is reduced but without any correlation to the apoE4 isoform. Dementia 7, 273-278
205. Hahne, S., Nordstedt, C., Ahlin, A., and Nyback, H. (1997) Levels of cerebrospinal fluid apolipoprotein E in patients with Alzheimer's disease and healthy controls. Neurosci. Lett. 224, 99-102
206. Merched, A., Blain, H., Visvikis, S., Herbeth, B.,Jeandel, C., and Siest, G. (1997) Cerebrospinal fluid apolipoprotein E level is increased in late-onset Alzheimer's disease. J. Neurol. Sci. 145, 33-39
207. Blomberg, M., Jensen, M., Basun, H., Lannfelt, L., and Wahlund, L. O. (1996) Increasing cerebrospinal fluid tau levels in a subgroup of Alzheimer patients with apolipoprotein E allele epsilon 4 during 14 months follow-up. Neurosci. Lett, 214, 163-166
208. + channels. Science 264, 276-279
209. Vestling, M., Adem, A., Racchi, M., Gibson, G. E., Lannfelt, L., and Cowburn, R. F. (1997) Differential regulation of adenylyl cyclase in fibroblasts from sporadic and familial Alzheimer's disease cases with PS1 and APP mutations. Neuroreport 8, 127-130
210. Rosenberg, R. N., Baskin, F., Fosmire, J. A., Risser, R., Adams, P., Svetlik, D., Honig, L. S., Cullum, M. C., and Weiner, M. F. (1997) Altered amyloid processing in platelets of patients with Alzheimer's disease. Arch. Neurol. 54, 139-144