Transgenic models of neurodegenerative diseases

Current Opinion in Neurobiology

Volumn 6, Issue 5, 1996, Pages 651-660

  Lee, Michael K ^a   Borchelt, David R ^a   Wong, Philip C ^a   Sisodia, Sangram S ^a   Price, Donald L ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APOLIPOPROTEIN E4; TRINUCLEOTIDE;

ALZHEIMER DISEASE; ANIMAL MODEL; AUTOSOMAL DOMINANT INHERITANCE; DEGENERATIVE DISEASE; GENE MUTATION; HUNTINGTON CHOREA; MOTOR NEURON DISEASE; MOUSE; NONHUMAN; PRION DISEASE; PRIORITY JOURNAL; REVIEW; TRANSGENIC ANIMAL;

EID: 0030273627     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(96)80099-7     Document Type: Article

References (115)

1. Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Dent H-X, et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science. 264:1994;1772-1775.
2. of outstanding interest Ripps ME, Huntley GW, Hof PR, Morrison JH, Gordon JW. Transgenic mice expressing an altered murine superoxide dismutase gene provide an animal model of amyotrophic lateral sclerosis. Proc Natl Acad Sci USA. 92:1995;689-693 A transgenic mouse that expresses murine SOD1 with a mutation analogous to the G85R FALS mutation develops MND at 3-4 months of age. Unlike other SOD1 transgenic mice that develop MND, the expression of G85R SOD1 does not lead to an increase in total SOD1 activity, and the normal level of SOD1 activity is maintained. Further, unlike other SOD1 transgenic mice, pathology in motor neurons is not characterized by vacuolar degeneration, indicating that vacuolar degeneration is not a required event in mutant SOD1-mediated MND.
3. of outstanding interest Wong PC, Pardo CA, Borchelt DR, Lee MK, Copeland NG, Jenkins NA, Sisodia SS, Cleveland DW, Price DL. An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron. 14:1995;1105-1116 A series of transgenic mice expressing high levels of wt HuSOD1 or mutant G37R SOD1 is generated. Mice that express G37R SOD1 develop MND with an age of onset and progression of disease that correlates with the level of transgene expression. MND is characterized by initial gliosis and vacuolar degeneration of mitochondria.
4. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, Carr T, Clemens J, Donaldson T, Gillespie F, et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature. 373:1995;523-527.
5. Hsiao KK, Scott M, Foster D, Groth DF, Dearmond SJ, Prusiner SB. Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science. 250:1990;1587-1590.
6. of outstanding interest Burright EN, Clark HB, Servadio A, Matilla T, Feddersen RM, Yunis WS, Duvick LA, Zoghbi HY, Orr HT. SCA1 transgenic mice: a model for neurodegeneration caused by an expanded CAG trinucleotide repeat. Cell. 82:1995;937-948 Transgenic mice that harbor a transgene encoding that HuSCA-I gene are generated using a strategy that directs high expression in Purkinje cells. High-level expression of the mutant gene with the expanded polyglutamine tract, but not the wt with the normal number of glutamines, causes degeneration of Purkinje cells in these mice by 30-40 weeks of age, resulting in ataxia.
7. Oppenheimer DR, Esiri MM. Diseases of the basal ganglia, cerebellum and motor neurons. Adams JH, Duchen LW. edn 5 Greenfields Neuropathology. 1992;988-1045 Oxford University Press, New York.
8. Siddique T, Pericak-Vance MA, Brooks BR, Roos RP, Hung W-Y, Antel JP, Munsat TL, Phillips K, Warner K, Speer M, et al. Linkage analysis in familial amyotrophic lateral sclerosis. Neurology. 39:1989;919-925.
9. Siddique T, Figlewicz DA, Pericak-Vance MA, Haines JL, Rouleau G, Jeffers AJ, Slapp P, Hung W-Y, Bebout J, McKenna-Yasek D, et al. Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity. N Engl J Med. 324:1991;1381-1384.
10. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, Oregan JP, Deng H-X, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 362:1993;59-62.
11. Deng H-X, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung W-Y, Getzoff ED, Hu P, Herzfeldt B, Roos RP. Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase. Science. 261:1993;1047-1051.
12. Carri MT, Battistoni A, Polizio F, Desideri A, Rotilio G. Impaired copper binding by the H46R mutant of human Cu,Zn superoxide dismutase, involved in amyotrophic lateral sclerosis. FEBS Lett. 356:1994;314-316.
13. Enayat ZE, Orrell RW, Claus A, Ludolph A, Bachus R, Brockmüller J, Ray-Chaudhuri K, Radunovic A, Shaw C, Wilkinson J. Two novel mutations in the gene for copper zinc superoxide dismutase in UK families with amyotrophic lateral sclerosis. Hum Mol Genet. 4:1995;1239-1240.
14. Halliwell B. Oxygen radicals as key mediators in neurological disease: fact or fiction? Ann Neurol. 32:1992;S10-S15.
15. Stadtman ER. Protein oxidation and aging. Science. 257:1992;1220-1224.
16. Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA. 87:1990;1620-1624.
17. Verge VMK, Xu Z, Xu X-J, Wiesenfeld-Hallin Z, Hökfelt T. Marked increase in nitric oxide synthase mRNA in rat dorsal root ganglia after peripheral axotomy: in situ hybridization and functional studies. Proc Natl Acad Sci USA. 89:1992;11617-11621.
18. Lipton SA, Choi Y-B, Pan Z-H, Lei SZ, Chen H-SV, Sucher NJ, Loscalzo J, Singel DJ, Stamler JS. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature. 364:1993;626-632.
19. Bowling AC, Schulz JB, Brown RH Jr, Beal MF. Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis. J Neurochem. 61:1993;2322-2325.
20. Robberecht W, Sapp P, Viaene MK, Rosen D, McKenna-Yasek D, Haines J, Horvitz R, Theys P, Brown R Jr. Cu/Zn superoxide dismutase activity in familial and sporadic amyotrophic lateral sclerosis. J Neurochem. 62:1994;384-387.
21. Chary P, Dillon D, Schroeder AL, Natvig DO. Superoxide dismutase (sod-1) null mutants of Neurospora crassa: oxidative stress sensitivity, spontaneous mutation rate and response to mutagens. Genetics. 137:1994;723-730.
22. Orr WC, Sohal RS. Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science. 263:1994;1128-1130.
23. Reveillaud I, Phillips J, Duyf B, Hilliker A, Kongpachith A, Fleming JE. Phenotypic rescue by a bovine transgene in a Cu/Zn superoxide dismutase-null mutant of Drosophila melanogaster. Mol Cell Biol. 14:1994;1302-1307.
24. Rothstein JD, Bristol LA, Hosler B, Brown RH Jr, Kuncl RW. Chronic inhibition of superoxide dismutase produces apoptotic death of spinal neurons. Proc Natl Acad Sci USA. 91:1994;4155-4159.
25. Troy CM, Shelanski ML. Down-regulation of copper/zinc superoxide dismutase causes apoptotic death in PC12 neuronal cells. Proc Natl Acad Sci USA. 91:1994;6384-6387.
26. of special interest Greenlund LJS, Deckwerth TL, Johnson EM Jr. Superoxide dismutase delays neuronal apoptosis: a role for reactive oxygen species in programmed neuronal death. Neuron. 14:1995;303-315 Using microinjection of SOD1 protein and insertion of an SOD1 expression plasmid into sympathetic neurons, the authors show that increased cellular levels of SOD1 delay neuronal death following withdrawal of nerve growth factor (NGF). The maximal level of SOD1-dependent protection of neurons from cell death approaches that obtained from the increased expression of bcl-2, a classic anti-apoptosis gene.
27. of outstanding interest Rabizadeh S, Butler Gralla E, Borchelt DR, Gwinn R, Selverstone Valentine J, Sisodia S, Wong P, Lee M, Hahn H, Bredesen DE. Mutations associated with amyotrophic lateral sclerosis convert superoxide dismutase from an antiapoptotic gene to a proapoptotic gene: studies in yeast and neural cells. Proc Natl Acad Sci USA. 92:1995;3024-3028 The increased expression of wt HuSOD1 in a neural cell lines leads to protection from apoptotic cell death. However, the expression of HuSOD1 with FALS mutations, despite significant increases in total SOD1 activity, promotes the apoptotic death of cells. The superoxide-scavenging activity of mutant SOD1 is also confirmed by the ability of mutant HuSOD1 to support the growth of the sod1 yeast strain in oxygen. The results support the hypothesis that SOD1 with FALS mutations causes disease via the dominant gain of deleterious properties.
28. of special interest Cleveland DW, Laing N, Hurse PV, Brown RH Jr. Toxic mutants in Charcots sclerosis. Nature. 378:1995;342-343 Levels of SOD1 activity in the blood of individuals with FALS with SOD1 mutations are compared to the age of onset of disease for each SOD1 mutant pedigree. The results show no significant correlation between SOD1 levels and the severity of disease.
29. Borchelt DR, Lee MK, Slunt HH, Guarnieri M, Xu Z-S, Wong PC, Brown RH Jr, Price DL, Sisodia SS, Cleveland DW. Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc Natl Acad Sci USA. 91:1994;8292-8296.
30. of outstanding interest Borchelt DR, Guarnieri M, Wong PC, Lee MK, Slunt HS, Xu Z, Sisodia SS, Price DL, Cleveland DW. Superoxide dismutase 1 subunits with mutations linked to familial amyotrophic lateral sclerosis do not affect wild-type subunit function. J Biol Chem. 270:1995;3234-3238 Using DNA transfection of cultured cells, the biochemical effects of FALS-mutant HuSOD1 expression on wt SOD1 are examined in a cellular context. The results show that the mutant SOD1 subunits, even when stably heterodimerized with wt SOD1, affect neither the activity nor the polypeptide stability of wt SOD1 subunits.
31. 2+ chelator.
32. of outstanding interest Reaume AG, Elliott JL, Hoffman EK, Kowall NW, Ferrante RJ, Siwek DF, Wilcox HM, Flood DG, Beal MF, Brown RH Jr, et al. Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nature Genet. 13:1996;43-47 Using gene-targeting technology, mice that lack a functional SOD1 gene are generated. To the surprise of many, the mice that lack SOD1 protein develop and mature normally. More importantly, the mice do not develop MND. However, when neurons are challenged by axotomy, a modest increase in the number of degenerated neurons is observed in SOD1 null mice.
33. of special interest Rooke K, Figlewicz DA, Han F-Y, Rouleau GA. Analysis of the KSP repeat of the neurofilament heavy subunit in familial amyotrophic lateral sclerosis. Neurology. 46:1996;789-790 Analyses of FALS pedigrees for mutations in the tail domain of the NF-H gene fail to find mutations specific to disease.
34. Brooks BP, Fischbeck KH. Spinal and bulbar muscular atrophy: a trinucleotide-repeat expansion neurodegenerative disease. Trends Neurosci. 18:1995;459-461.
35. of special interest Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 80:1995;155-165 Using positional cloning methods, a gene deleted in -95% of spinal muscular atrophy (SMA) patients is identified. This gene named survival motor neuron (SMN), encodes a novel protein of approximately 32 kDa. Although SMN is at least partially deleted in a large majority of patients with SMA, a nearby gene termed cBCD541, which encodes an identical protein, is never deleted.
36. of special interest Roy N, Mahadevan MS, McLean M, Shutler G, Yaraghi Z, Farahani R, Baird S, Besner-Johnston A, Lefebvre C, Kang X. The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy. Cell. 80:1995;167-178 Analyses of a region deleted in SMA led to the identification of a gene termed neuronal apoptosis inhibitory protein (NAIP). The encoded polypeptide shares homology with an insect antiapoptosis protein, an inhibitor of apoptosis protein (iap). Analyses of patients with SMA show that NAIP is deleted in more than 50% of patients with the severest form of the disease. A more detailed analysis of the NAIP gene in cases of SMA is hampered by the fact that multiple copies of NAIP-like genes are present in the human genome.
37. Dal Canto MC, Gurney ME. Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis. Am J Pathol. 145:1994;1271-1280.
38. of special interest Mourelatos Z, Gonatas NK, Stieber A, Gurney ME, Dal Canto MC. The Golgi apparatus of spinal cord motor neurons in transgenic mice expressing mutant Cu,Zn superoxide dismutase becomes fragmented in early, preclinical stages of the disease. Proc Natl Acad Sci USA. 93:1996;5472-5477 The authors show that the Golgi apparatus is disrupted in spinal motor neurons from transgenic mice expressing G93A mutant SOD1. Golgi fragmentation seems to be an early indication of motor neuron defects.
39. of special interest Tu P-H, Raju P, Robinson KA, Gurney ME, Trojanowski JQ, Lee VM-Y. Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions. Proc Natl Acad Sci USA. 93:1996;3155-3160 Immunocytochemical examination of transgenic mice that express the G93A HuSOD1 mutation reveals the development of NF-rich spheroids and Lewy body-like inclusions in spinal motor neurons. The authors conclude that SOD1 transgenic mice develop neuronal cytoskeletal abnormalities similar to those seen in human ALS. The results implicate neuronal cytoskeletal components as targets of mutant SOD1-mediated damage.
40. Beckman JS, Carson M, Smith CD, Kopenhol WH. ALS, SOD and peroxynitrite. Nature. 364:1993;584.
41. of special interest Pardo CA, Xu Z, Borchelt DR, Price DL, Sisodia SS, Cleveland DW. Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons. Proc Natl Acad Sci USA. 92:1995;954-958 Using highly specific anti-SOD1 rabbit polyclonal antibodies, SOD1 expression is examined in neural tissues. Immunocytochemical analysis shows high levels of SOD1 expression in a variety of neurons, including hippocampal pyramidal neurons and spinal motor neurons. Immunoelectron microscopic analysis localizes SOD1 to the cytosol, nucleus, and membranous organelles.
42. Liu XF, Cizewski Culotta V. The requirement for yeast superoxide dismutase is bypassed through mutations in BSD2, a novel metal homeostasis gene. Mol Cell Biol. 14:1994;7037-7045.
43. Lapinskas PJ, Cunningham KW, Liu XF, Fink GR, Cizewski Culotta V. Mutations in PMR1 suppress oxidative damage in yeast cells lacking superoxide dismutase. Mol Cell Biol. 15:1995;1382-1388.
44. Wong PC, Borchelt DR. Motor neuron disease caused by mutations in superoxide dismutase 1. Curr Opin Neurol. 8:1995;294-301.
45. Hoffman PN, Thompson GW, Griffin JW, Price DL. Changes in neurofilament transport coincide temporally with alterations in the caliber of axons in regenerating motor fibers. J Cell Biol. 101:1985;1332-1340.
46. Hoffman PN, Cleveland DW, Griffin JW, Landes PW, Cowan NJ, Price DL. Neurofilament gene expression: a major determinant of axonal caliber. Proc Natl Acad Sci USA. 84:1987;3472-3476.
47. Eyer J, Peterson A. Neurofilament-deficient axons and perikaryal aggregates in viable transgenic mice expressing a neurofilament-β-galactosidase fusion protein. Neuron. 12:1994;389-405.
48. Carpenter S. Proximal axonal enlargement in motor neuron disease. Neurology. 18:1968;841-851.
49. Clark AW, Parhad IM, Griffin JW, Price DL. Neurofilamentous axonal swellings as a normal finding in the spinal anterior horn of man and other primates. J Neuropathol Exp Neurol. 43:1984;253-262.
50. Schmidt ML, Carden MJ, Lee VM-Y, Trojanowski JQ. Phosphate dependent and independent neurofilament epitopes in the axonal swellings of patients with motor neuron disease and controls. Lab Invest. 56:1987;282-294.
51. Hirano A, Kato S. Fine structural study of sporadic and familial amyotrophic lateral sclerosis. Smith RA. Handbook of Amyotrophic Lateral Sclerosis. 1992;183-192 Marcel Dekker, New York.
52. Griffin JW, Hoffman PN, Clark AW, Carroll PT, Price DL. Slow axonal transport of neurofilament proteins: impairment by β,β'-iminodipropionitrile administration. Science. 202:1978;633-635.
53. Cork LC, Struble RG, Gold BG, Dicarlo C, Fahnestock KE, Griffin JW, Price DL. Changes in size of motor axons in Hereditary Canine Spinal Muscular Atrophy. Lab Invest. 61:1989;333-342.
54. Muma NA, Cork LC. Alterations in neurofilament mRNA in hereditary canine spinal muscular atrophy. Lab Invest. 69:1993;436-442.
55. Xu Z, Cork LC, Griffin JW, Cleveland DW. Increaased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell. 73:1993;23-33.
56. Coté 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. 73:1993;35-46.
57. of outstanding interest Collard J-F, Coté F, Julien J-P. Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis. Nature. 375:1995;61-64 Transgenic mice that express high levels of HuNF-H show a significant slowing of transport rates for cytoskeletal proteins and severe reduction in the overall diameter of axons, without significant axonal degeneration. Immunocytochemical and electron microscopic analyses are interpreted to show that the transport of mitochondria is severely affected and that these organelles are largely excluded from axoplasm. The authors conclude that abnormalities in axonal transport may provide a mechanistic explanation for MND in ALS.
58. Lee MK, Marszalek JR, Cleveland DW. A mutant neurofilament subunit causes massive, selective motor neuron death: implications for the pathogenesis of human motor neuron disease. Neuron. 13:1994;975-988.
59. Bachman DL, Wolf PA, Linn RT, Knoefel JE, Cobb JL, Belander AJ, White LR, Dagostino RB. Incidence of dementia and probable Alzheimer's disease in a general population: the Framingham study. Neurology. 43:1993;515-519.
60. Ernst RL, Hay JW. The US economic and social costs of Alzheimer's disease revisited. Am J Public Health. 84:1994;1261-1264.
61. of special interest St George-Hyslop PH, Haines P, Rogaev E, Mortilla M, Vaula G, Pericak-Vanca M, Foncin J-F, Montesi M, Bruni A, Sorbi S, et al. Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14. Nat Genet. 2:1992;330-334.
62. The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Nat Genet. 11:1995;219-222 The authors report on new FAD-linked mutations on PS1 gene. They also present the intron/exon organization of the PS1 gene.
63. of outstanding interest Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature. 375:1995;754-760 Genetic linkage and DNA cloning studies of chromosome 14 FAD locus reveals a novel gene termed S182 (PS1). The S182 gene encodes a novel multiple transmembrane protein and missense mutations in S182 gene cosegregate with early-onset FAD.
64. of special interest Wasco W, Pettingell WP, Jondro PD, Schmidt SD, Gurubhagavatula S, Rodes L, Diblasi T, Romano DM, Guenette SY, Kovacs DM, Growdon JH, Tanzi RE. Familial Alzheimer's chromosome 14 mutations. Nat Med. 1:1995;848 A short letter in which the authors report on their identification of FAD-linked mutations on PS1.
65. of outstanding interest Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu C-E, Jondro PD, Schmidt SD, Wang K, et al. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science. 269:1995;973-977 Study identifying the candidate gene for the chromosome 1 linked FAD. The STM2 (PS2) gene encodes a protein highly homologous to that encoded by chromosome 14 linked FAD gene (S182 or PS1).
66. of special interest Levy-Lahad E, Wijsman EM, Nemens E, Anderson L, Goddard KAB, Weber JL, Bird TD, Schellenberg GD. A familial Alzheimer's disease locus on chromosome 1. Science. 269:1995;970-973 Genetic linkage study showing that FAD in the Volga - German kindreds are linked to a locus on chromosome 1q31-42.
67. of outstanding interest Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T, et al. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature. 376:1995;775-778 Study showing cloning of a novel gene (E5-1 or PS2) on chromosome 1 that shares homology to S182 (PS1) gene on chromosome 14. Mutations in E5-1 are linked to early-onset FAD with a later onset than te chromosome 14 linked FAD.
68. 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. 353:1991;844-846.
69. Goate A, Chartier-Harlin M-C, Mullan M, Brown J, Crawford F, Fidani L, Giuffra L, Haynes A, Irving N, James L, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature. 349:1991;704-706.
70. Hendricks L, Van Duijn CM, Cras P, Cruts M, Van Hul W, Van Harskamp F, Warren A, McInnis MG, Antonarakis SE, Martin J-J. Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β-amyloid precursor protein gene. Nat Genet. 1:1992;218-221.
71. Mullan M, Crawford F, Axelman K, Houlden H, Lillius 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. 1:1992;345-347.
72. Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA. Gene dose of apoliprotein-E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 261:1993;921-923.
73. Roses AD. Apolipoprotein E affects the rate of Alzheimer disease expression: β-amyloid burden is a secondary consequence dependent on APOE genotype and duration of disease. J Neuropathol Exp Neurol. 53:1994;429-437.
74. of outstanding interest Thinakaran G, Borchelt DR, Lee MK, Slunt HH, Spitzer L, Kim G, Ratovitsky T, Davenport F, Nordstedt C, Seeger M. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron. 17:1996;181-190 Analysis of cultured cells and transgenic mice expressing PS1 protein using two highly specific anti-PS1 antibodies. The study documents that PS1 protein is endoproteolytically processed in vivo and that accumulation of processed fragments are regulated.
75. of outstanding interest Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, Bird TD, Hardy J, Hutton M, Kukull W, et al. The amyloid β protein deposited 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. Nature Med. 2:1996;864-870 The study shows increased levels of highly amyloidogenic Aβ-peptide ending at Aβ42(43) in plasma from individuals harbouring PS1, PS2 and APP mutations linked to FAD. The study also shows that the fibroblasts established from individuals harbouring presenilin mutations secrete more Aβ42(43) compared to less amyloidogenic Aβ40. These results suggest that mutations in presenilins may lead to AD pathology by increased pathogenic processing of APP.
76. Levy E, Carman MD, Fernandez-Madrid U, Power MD, Lieberburg I, Van Duinen SG, Bots GTAM, Luyendijk W, Frangione B. Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science. 248:1990;1124-1126.
77. Van Broeckhoven C, Haan J, Bakker E, Hardy JA, Van Hul W, Wehnert A, Vegter-Van Der Vlis M, Roos RAC. Amyloid β protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch). Science. 248:1990;1120-1122.
78. Citron M, Ottersdorf T, Haass C, McConlogue L, Hung AY, Seubert P, Vigo-Pelfrey C, Lieberburg I, Selkoe DJ. Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production. Nature. 360:1992;672-674.
79. Cai X-D, Golde TE, Younkin SG. Release of excess amyloid β protein from a mutant amyloid β protein precursor. Science. 259:1993;514-516.
80. Thinakaran G, Teplow DB, Siman R, Greenberg B, Sisodia SS. Metabolism of the `Swedish APP' variant in Neuro2A (N2a) cells: evidence that cleavage at the `β-secretase' site occurs in the Golgi apparatus. J Biol Chem. 271:1996;9390-9397.
81. 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. 179:1991;1247-1254.
82. Haass C, Hung AY, Selkoe DJ, Teplow DB. Mutations associated with a locus for familial Alzheimer's disease result in alternative processing of amyloid β-protein precursor. J Biol Chem. 269:1994;17741-17748.
83. 717) mutants. Science. 264:1994;1336-1340.
84. Burdick D, Soreghan B, Kwon M, Kosmoski J, Knauer M, Henschen A, Yates J, Cotman C, Glabe C. Assembly and aggregation properties of synthetic Alzheimer's A4/β amyloid peptide analogs. J Biol Chem. 267:1992;546-554.
85. Jarrett JT, Lansbury PT Jr. Seeding `one-dimensional' crystallization of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie? Cell. 73:1993;1055-1058.
86. Jarrett JT, Berger EP, Lansbury PT Jr. 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. 32:1993;4693-4697.
87. Iwatsubo T, Odaka A, Suzuki N, Mizusawa H, Nukina N, Ihara Y. Visualization of Aβ42(43)-positive and Aβ40-positive senile plaques with end-specific Aβ-monoclonal antibodies: evidence that an initially deposited A species is Aβ1-42(43). Neuron. 13:1994;45-53.
88. Lemere CA, Blusztajn JK, Yamaguchi H, Wisniewski T, Saido TC, Selkoe DJ. Sequence of deposition of heterogeneous amyloid β-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol Dis. 3:1996;16-32.
89. Mayeux R, Stern Y, Ottman R, Tatemichi TK, Tang M-X, Maestre G, Ngai C, Tycko B, Ginsberg H. The apolipoprotein ε4 allele in patients with Alzheimer's disease. Ann Neurol. 34:1993;752-754.
90. Poirier J, Davignon J, Bouthilier D, Kogan S, Bertrand P, Gauthier S. Apolipoprotein E polymorphism and Alzheimer's disease. Lancet. 342:1993;697-699.
91. Rebeck GW, Reiter JS, Strickland DK, Hyman BT. Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions. Neuron. 11:1993;575-580.
92. Saunders AM, Strittmatter WJ, Schmechel D, St George-Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper-MacLachlan DR, Alberts MJ, et al. Association of apolipoprotein E allele ε4 with late-onset familial and sporadic Alzheimer's disease. Neurology. 43:1993;1467-1472.
93. Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD. 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. 90:1993;1977-1981.
94. Chartier-Harlin M-C, Parfitt M, Legrain S, Perez-Tur J, Brousseau T, Evans A, Berr C, Vidal O, Roques P, Gourlet V, et al. Apolipoprotein E, ε4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region. Hum Mol Genet. 3:1994;569-574.
95. Tsai M-S, Tangalos EG, Petersen RC, Smith GE, Schaid DJ, Kokmen E, Ivnik RJ, Thibodeau SN. Apolipoprotein E: risk factor for Alzheimer disease. Am J Hum Genet. 54:1994;643-649.
96. Hendrie HC, Hall KS, Hui S, Unverzagt FW, Yu CE, Lahiri DK, Sahota A, Farlow M, Musick B, Class CA, et al. Apolipoprotein E genotypes and Alzheimer's disease in a community study of elderly African Americans. Ann Neurol. 37:1995;118-120.
97. Price DL, Sisodia SS. Cellular and molecular biology of Alzheimer's disease and animal models. Annu Rev Med. 45:1994;435-446.
98. Rockenstein EM, McConlogue L, Tan H, Power M, Masliah E, Mucke L. Levels and alternative splicing of amyloid β protein precursor (APP) transcripts in brains of APP transgenic mice and humans with Alzheimer's disease. J Biol Chem. 270:1995;28257-28267.
99. Prusiner SB, Hsiao KK. Human prion diseases. Ann Neurol. 35:1994;385-395.
100. Borchelt DR, Scott M, Taraboulos A, Stahl N, Prusiner SB. Scrapie and cellular prion proteins differ in their kinetics of synthesis and topology in cultured cells. J Cell Biol. 110:1990;743-752.
101. Pan KM, Baldwin M, Nguyen J, Gasset M, Serban A, Groth D, Mehlhom I, Huang Z, Fletterick RJ, Cohen FE, Prusiner SB. Conversion of α-helices into β-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci USA. 90:1993;10962-10966.
102. Stahl N, Baldwin MA, Teplow DB, Hood L, Gibson BW, Burlingame AL, Prusiner SB. Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing. Biochemistry. 32:1993;1991-2002.
103. of special interest Riek R, Hornemann S, Wider G, Billeter M, Glockshuber R, Wüthrich K. NMR structure of the mouse prion protein domain PrP(121-231). Nature. 382:1996;180-182 This report describes the three-dimensional structure of a recombinant PrP polypeptide encompassing residues 121-231, a region that contains many of the mutations linked to familial prior disorders as well as species-specific variant residues thought to play a role in a phenomenon termed the species barrier.
104. Hsiao KK, Groth D, Scott M, Yang S-L, Serban H, Rapp D, Foster D, Torchia M, Dearmond SJ, Prusiner SB. Serial transmission in rodents in neurodegeneration from transgenic mice expressing mutant prion proteins. Proc Natl Acad Sci USA. 91:1994;9126-9130.
105. Sc).
106. Warren ST. The expanding world of trinucleotide repeats. Science. 271:1996;1374-1375.
107. Trottier Y, Lutz Y, Stevanin G, Imbert G, Devys D, Cancel G, Saudou F, Weber C, David G, Tora L, et al. Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxias. Nature. 378:1995;403-406.
108. Junck L, Fink JK. Machado-Joseph disease and SCA3: the genotype meets the phenotypes. Neurology. 46:1996;4-8.
109. Sharp AH, Ross CA. Neurobiology of Huntington's disease. Neurobiol Dis. 3:1996;3-15.
110. of outstanding interest Campuzano V, Montermini L, Molto MD, Pianese L, Cossée M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science. 271:1996;1423-1427 The genetic locus responsible for autosomal recessive Friedreich's ataxia is defined. Point mutations in the coding domain and expansions of a GAA repeat motif in the first intron are identified in individuals with the disease.
111. Persichetti F, Ambrose CM, Ge P, McNeil SM, Srinidhi J, Anderson MA, Jenkins B, Barnes GT, Duyao MP, Kanaley L, et al. Normal and expanded Huntington's disease gene alleles produce distinguishable proteins due to translation across the CAG repeat. Mol Med. 1:1995;374-383.
112. Bingham PM, Scott MO, Wang S, McPhaul MJ, Wilson EM, Garbern JY, Merry DE, Fischbeck KH. Stability of an expanded trinucleotide repeat in the androgen receptor gene in transgenic mice. Nat Genet. 9:1995;191-196.
113. Stott K, Blackburn JM, Butler PJG, Perutz M. Incorporation of glutamine repeats makes protein oligomerize: implications for neurodegenerative diseases. Proc Natl Acad Sci USA. 92:1995;6509-6513.
114. Li X-J, Li S-H, Sharp AH, Nucifora FC Jr, Schilling G, Lanahan A, Worley P, Snyder SH, Ross CA. A huntingtin-associated protein enriched in brain with implications for pathology. Nature. 378:1995;398-402.
115. Burke JR, Enghild JJ, Martin ME, Jou Y-S, Myers RM, Roses AD, Vance JM, Strittmatter WJ. Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH. Nature Med. 2:1996;347-350.