The solved and unsolved mysteries of the genetics of early-onset Alzheimer's disease

NeuroMolecular Medicine

Volumn 2, Issue 1, 2002, Pages 1-10

  Rogaeva, Ekaterina ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

Alzheimer's Disease; APP; Mutation; Presenelin

Indexed keywords

AMYLOID PRECURSOR PROTEIN; PRESENILIN 1; PRESENILIN 2; APOLIPOPROTEIN E; APOLIPOPROTEIN E4; ASPARTIC PROTEINASE; BACE1 PROTEIN, HUMAN; MEMBRANE PROTEIN; NERVE PROTEIN; PROTEINASE; PSEN1 PROTEIN, HUMAN; PSEN2 PROTEIN, HUMAN; SECRETASE;

ALZHEIMER DISEASE; AUTOSOMAL DOMINANT DISORDER; CLINICAL RESEARCH; DISEASE ASSOCIATION; EARLY DIAGNOSIS; GENE IDENTIFICATION; GENE MUTATION; GENETIC ANALYSIS; GENETIC DISORDER; GENETIC HETEROGENEITY; HUMAN; ONSET AGE; PATHOPHYSIOLOGY; PEDIGREE ANALYSIS; PRIORITY JOURNAL; REVIEW; ADULT; AGED; CHROMOSOME 14; CHROMOSOME 21; DOMINANT GENE; FORECASTING; GENETIC EPISTASIS; GENETIC PREDISPOSITION; GENETIC SCREENING; GENETICS; METABOLISM; MIDDLE AGED; PEDIGREE; PHENOTYPE; PROTEIN PROCESSING; SPASTIC PARAPLEGIA;

ADULT; AGE OF ONSET; AGED; ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; AMYLOID PRECURSOR PROTEIN SECRETASES; APOLIPOPROTEIN E4; APOLIPOPROTEINS E; ASPARTIC ENDOPEPTIDASES; CHROMOSOMES, HUMAN, PAIR 14; CHROMOSOMES, HUMAN, PAIR 21; ENDOPEPTIDASES; EPISTASIS, GENETIC; FORECASTING; GENES, DOMINANT; GENETIC HETEROGENEITY; GENETIC PREDISPOSITION TO DISEASE; GENETIC SCREENING; HUMANS; MEMBRANE PROTEINS; MIDDLE AGED; NERVE TISSUE PROTEINS; PARAPARESIS, SPASTIC; PEDIGREE; PHENOTYPE; PRESENILIN-1; PRESENILIN-2; PROTEIN PROCESSING, POST-TRANSLATIONAL;

EID: 0036364359     PISSN: 15351084     EISSN: None     Source Type: Journal    
DOI: 10.1385/nmm:2:1:01     Document Type: Review

References (71)

1. Acquati, F., Accarino, M., Nucci, C., Fumagalli, P., Jovine, L., Ottolenghi, S., and Taramelli, R. (2000) The gene encoding DRAP (BACE2), a glycosylated transmembrane protein of the aspartic protease family, maps to the down critical region. FEBS Lett. 468,59-64.
2. Amtul, Z., Lewis, P. A., Piper, S., Crook, R., Baker, M., Findlay, K., et al. (2002) A Presenilin 1 mutation associated with familial frontotemporal dementia inhibits gamma-secretase cleavage of APP and Notch. Neurobiol. Dis. 9, 269-273.
3. Ancolio, K., Dumanchin, C., Barelli, H., Warter, J. M., Brice, A., Campion, D., et al. (1999) Unusual phenotypic alteration of beta amyloid precursor protein (betaAPP) maturation by a new Val-715 → Met betaAPP-770 mutation responsible for probable early-onset Alzheimer's disease. Proc. Natl. Acad. Sci. USA 96, 4119-4124.
4. Athan, E. S., Williamson, J., Ciappa, A., Santana, V., Romas, S. N., Lee, J. H., et al. (2001) A founder mutation in presinilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families. JAMA 286: 2257-2263.
5. Bennett, B. D., Babu-Khan, S., Loeloff, R., Louis, J. C., Curran, E., Citron, M., and Vassar, R. (2000) Expression analysis of BACE2 in brain and peripheral tissues. J. Biol. Chem. 275, 20647-20651.
6. Bird, T. D., Levy-Lahad, E., Poorkaj, P., Sharma, V., Nemens, E., Lahad, A., et al. (1996) Wide range in age of onset for chromosome 1-related familial Alzheimer's disease. Ann. Neurol. 40, 932-936.
7. Capell, A., Steiner, H., Romig, H., Keck, S., Baader, M., Grim, M. G., et al. (2000) Presenilin-1 differentially facilitates endoproteolysis of the beta-amyloid precursor protein and Notch. Nat. Cell Biol. 2, 205-211.
8. Checler, F. (2001) The multiple paradoxes of presenilins. J. Neurochem. 76, 1621-1627.
9. Citron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A. Y., Seubert, P., et al. (1992) Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. Nature 360, 672-674.
10. Citron, M., Vigo-Pelfrey, C., Teplow, D. B., Miller, C., Schenk, D., Johnston, J., et al. (1994) Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation. Proc. Natl. Acad. Sci. USA 91, 11993-11997.
11. Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., et al. (1997) Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid beta-protein in both transfected cells and transgenic mice. Nat. Med. 3, 67-72.
12. Crook, R., Verkkoniemi, A., Perez-Tur, J., Mehta, N., Baker, M., Houlden, H., et al. (1998) A variant of Alzheimer's disease with spastic paraparesis and unusual plaques due to deletion of exon 9 of presenilin 1. Nat. Med. 4, 452-455.
13. Cruts, M., van Duijn, C. M., Backhovens, H., Van den, B. M., Wehnert, A., Serneels, S., et al. (1998) Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease. Hum. Mol. Genet. 7, 43-51.
14. Cruts, M., Dermaut, B., Rademakers, R., Roks, G., Van den Broeck, M., Munteanu, G., et al. (2001) Amyloid beta secretase gene (BACE) is neither mutated in nor associated with early-onset Alzheimer's disease. Neurosci. Lett. 313, 105-107.
15. De Strooper, B., Annaert, W., Cupers, P., Saftig, P., Craessaerts, K., Mumm, J. S., et al. (1999) A presinilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518-522.
16. Dermaut, B., Theuns, J., Sleegers, K., Hasegawa, H., Van den Broeck, M., Vennekens, K., et al. (2002) The gene encoding nicastrin, a major γ-secretase component, modifies risk for familial early-onset Alzheimer's disease in a Dutch population-based sample. Am. J. Hum. Genet., submitted.
17. Eckman, C. B., Mehta, N. D., Crook, R., Perez-tur, J., Prihar, G., Pfeiffer, E., et al. (1997) A new pathogenic mutation in the APP gene (1716V) increases the relative proportion of A beta 42(43). Hum. Mol. Genet. 6, 2087-2089.
18. Farrer, L. A., Cupples, L. A., Haines, J. L., Hyman, B., Kukull, W. A., Mayeux, R., et al. (1997) Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A metaanalysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA 278, 1349-1356.
19. Goate, A., Chartier-Harlin, M. C., Mullan, M., Brown, J., Crawford, F., Fidani, L., et al. (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349, 704-706.
20. Gotz, J., Chen, F., van Dorpe, J., and Nitsch, R. M. (2001) Formation of neurofibrillary tangles in P3011 tau transgenic mice induced by Abeta 42 fibrils. Science 293, 1491-1495.
21. Haass, C., Hung, A. Y., Selkoe, D. J., and Teplow, D. B. (1994) Mutations associated with a locus for familial Alzheimer's disease result in alternative processing of amyloid beta-protein precursor. J. Biol. Chem. 269, 17741-17748.
22. Hardy, J. A. and Higgins, G. A. (1992) Alzheimer's disease: the amyloid cascade hypothesis. Science 256, 184-185.
23. Hardy, J. (1997) Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci. 20, 154-159.
24. Hiltunen, M., Helisalmi, S., Mannermaa, A., Alafuzoff, I., Koivisto, A. M., Lehtovirta, M., et al. (2000) Identification of a novel 4.6-kb genomic delition in presenilin-1 gene which results in exclusion of exon 9 in a Finnish early onset Alzheimer's disease family: an Alu core sequence-stimulated recombination? Eur. J. Hum. Genet. 8, 259-266.
25. Houlden, H., Crook, R., Backhovens, H., Prihar, G., Baker, M., Hutton, M., et al. (1998) ApoE genotype is a risk factor in nonpresenilin early-onset Alzheimer's disease families. Am. J. Med. Genet. 81, 117-121.
26. Houlden, H., Baker, M., McGowan, E., Lewis, P., Hutton, M., Crook, R., et al. (2000) Variant Alzheimer's disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-beta concentrations. Ann. Neurol. 48, 806-808.
27. Jarrett, J. T. and Lansbury, P. T., Jr. (1993) Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie? Cell 73, 1055-1058.
28. Kulic, L., Walter, J., Multhaup, G., Teplow, D. B., Baumeister, R., Romig, H., et al. (2000) Separation of presenilin function in amyloid beta-peptide generation and endoproteolysis of Notch. Proc. Natl. Acad. Sci. USA 97, 5913-5918.
29. Le, T. V., Crook, R., Hardy, J., and Dickson, D. W. (2001) Cotton wool plaques in non-familial late-onset Alzheimer disease. J. Neuropathol. Exp. Neurol. 60, 1051-1061.
30. Levitan, D., Doyle, T. G., Brousseau, D., Lee, M. K., Thinakaran, G., Slunt, H. H., et al. (1996) Assessment of normal and mutant presenilin function in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 93, 14, 940-14, 944.
31. Levy-Lahad, E., Wijsman, E. M., Nemens, E., Anderson, L., Goddard, K. A., Weber, J. L., et al. (1995) A familial Alzheimer's disease locus on chromosome 1. Science 269, 970-973.
32. Lewis, J., Dickson, D. W., Ling, W. L., Chisholm, L., Corral, A., Jones, G., et al. (2001) Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293, 1487-1491.
33. Mattila, K. M., Forsell, C., Pirttila, T., Rinne, J. O., Lehtimaki, T., Roytta, M., et al. (1998) The Glu318Gly mutation of the presenilin-1 gene does not necessarily cause Alzheimer's disease. Ann. Neurol. 44, 965-967.
34. Mizutani, T., Taniguchi, Y., Aoki, T., Hashimoto, N., and Honjo, T. (2001) Conservation of the biochemical mechanisms of signal transduction among mammalian Notch family members. Proc. Natl. Acad. Sci. USA 98, 9026-9031.
35. Modrek, B., Resch, A., and Grasso, C. (2001) Genomewide detection of alternative splicing in expressed sequences of human genes. Nucleic Acids Res. 29, 2850-2859.
36. Mullan, M., Crawford, F., Axelman, K., Houlden, H., Lilius, L., Winblad, B., and Lannfelt, L. (1992) A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid. Nat. Genet. 1, 345-347.
37. Myers, A., Wavrant De-Vrieze, F., Holmans, P., Hamshere, M., Crook, R., Compton, D., et al. (2002) Full genome screen for Alzheimer disease: Stage II analysis. Am. J. Med. Genet. 114, 235-244.
38. Ni, C. Y., Murphy, M. P., Golde, T. E., and Carpenter, G. (2001) gamma-Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science 294, 2179-2181.
39. Nicolaou, M., Song, Y. Q., Sato, C. A., Orlacchio, A., Kawarai, T., Medeiros, H., et al. (2001) Mutations in the open reading frame of the beta-site APP cleaving enzyme (BACE) locus are not a common cause of Alzheimer's disease. Neurogenetics 3, 203-206.
40. Nilsberth, C., Westlind-Danielsson, A., Christopher, B., Eckman, C. B., Forsell, C., and Axelm, K. (2001) The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Abeta protofibril formation. Nat. Neurosci. 4, 887-893.
41. Pericak-Vance, M. A., Bebout, J. L., Gaskell, P. C., Jr., Yamaoka, L. H., Hung, W. Y., Alberts, M. J., et al. (1991) Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am. J. Hum. Genet. 48, 1034-1050.
42. Podlisny, M. B., Citron, M., Amarante, P., Sherrington, R., Xia, W., Zhang, J., et al. (1997) Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N-and C-terminal fragments in normal and Alzheimer brain tissue. Neurobiol. Dis. 3, 325-337.
43. Poorkaj, P., Bird, T. D., Wijsman, E., Nemens, E., Garruto, R. M., Anderson, L., et al. (1998) Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol. 43, 815-825.
44. Rogaev, E. I., Sherrington, R., Rogaeva, E. A., Levesque, G., Ikeda, M., Liang, Y., et al. (1995) 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, 775-778.
45. Rogaeva, E. A., Fafel, K. C., Song, Y. Q., Medeiros, H., Liang, Y., Sato, C., et al. (2001) Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations. Neurology 57, 621-625.
46. Rogaeva, E. A., Moliaka, I., Kawarai, T., Sato, C., Medeiros, H., Song, Y.-Q., et al. (2002) A novel PS1 case of variant Alzheimer's disease with spastic paraplegia: the search for a gene-modifier. Ann. Neurol., submitted.
47. Roses, A. D. (1998) Apolipoprotein E and Alzheimer's disease. The tip of the susceptibility iceberg. Ann. NY Acad. Sci. 855, 738-743.
48. Saunders, A. M., Strittmatter, W. J., Schmechel, D., George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., et al. (1993) Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 43, 1467-1472.
49. Saxena, M. T., Schroeter, E. H., Mumm, J. S., and Kopan, R. (2001) Murine notch homologs (N1-4) undergo presenilin-dependent proteolysis. J. Biol. Chem. 276, 40268-40273.
50. Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M,. Suzuki, N., et al. (1996) Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presinilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat. Med. 2, 864-870.
51. Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., et al. (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375, 754-760.
52. Sherrington, R., Froelich, S., Sorbi, S., Campion, D., Chi, H., Rogaeva, E. A., et al. (1996) Alzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant. Hum. Mol. Genet. 5, 985-988.
53. Shoji, M., Gold, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M., et al. (1992) Production of the Alzheimer amyloid beta protein by normal proteolytic processing. Science 258, 126-129.
54. Smith, M. J., Kwok, J. B., McLean, C. A., Kril, J. J., Broe, G. A., Nicholson, G. A., et al. (2001) Variable phenotype of Alzheimer's disease with spastic paraparesis. Ann. Neurol. 49, 125-129.
55. Song, W., Nadeau, P., Yuan, M., Yang, X., Shen, J., and Yankner, B. A. (1999) Proteolytic release and nuclear translocation of Notch-1 are induced by presenilin-1 and impaired by pathogenic presenilin-1 mutations. Proc. Natl. Acad. Sci. USA 96, 6959-6963.
56. Steiner, H., Duff, K., Capell, A., Romig, H., Grim, M. G., Lincoln, S., et al. (1999) A loss of function mutation of presenilin-2 interferes with amyloid beta-peptide production and notch signaling. J. Biol. Chem. 274, 28669-28673.
57. Steiner, H. and Haass, C. (2001) Nuclear signaling: a common function of presenilin substrates? J. Mol. Neurosci. 17, 193-198.
58. Steiner, H., Revesz, T., Neumann, M., Romig, H., Grim, M. G., Pesold, B., et al. (2001) A pathogenic presenilin-1 deletion causes abberrant A-beta-42 production in the absence of congophilic amyloid plaques. J. Biol. Chem. 276, 7233-7239.
59. St. George-Hyslop, P., McLachlan, D. C., Tsuda, T., Rogaev, E., Karlinsky, H., Lippa, C. F., et al. (1994) Alzheimer's disease and possible gene interaction. Science 263, 537.
60. St. George-Hyslop, P. H. (2000) Genetic factors in the genesis of Alzheimer's disease. Ann. NY Acad. Sci. 924, 1-7.
61. 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 beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 1977-1981.
62. Suzuki, N., Cheung, T. T., Cai, X. D., Odaka, A., Otvos, L., Jr., Eckman, C., et al. (1994) An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science 264, 1336-1340.
63. Tandon, A., Rogaeva, E. A., Mullan, M., and St. George-Hyslop, P. (2000) Molecular genetics of Alzheimer's disease: the role of beta-amyloid and the presenilins. Curr. Opin. Neurol. 13, 377-384.
64. Theuns, J. and Van Broeckhoven, C. (2000) Transcriptional regulation of Alzheimer's disease genes: implications for susceptibility. Hum. Mol. Genet. 9, 2383-2394.
65. Theuns, J., Del-Favero, J., Dermaut, B., van Duijn, C. M., Backhovens, H., Van den Broeck, M. V., et al. (2000) Genetic variability in the regulatory region of presenilin 1 associated with risk for Alzheimer's disease and variable expression. Hum. Mol. Genet. 9, 325-331.
66. Thinakarak, G., Borchelt, D. R., Lee, M. K., Slunt, H. H., Spitzer, L., Kim, G., et al. (1996) Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17, 181-190.
67. Van Broeckhoven, C., Backhovens, H., Cruts, M., Martin, J. J., Crook, R., Houlden, H., and Hardy, J. (1994) APOE genotype does not modulate age of onset in families with chromosome 14 encoded Alzheimer's disease. Neurosci. Lett. 169, 179-180.
68. Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., et al. (1999) beta-Secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735-741.
69. Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T., and Selkoe, D. J. (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 398, 513-517.
70. Yu, G., Nishimura, M., Arawaka, S., Levitan, D., Zhang, L., Tandon, A., et al. (2000) Nicastrin modulates presinilin-mediated notch/glp-1 signal transduction and betaAPP processing. Nature 407, 48-54.
71. Zhang, D. M., Levitan, D., Yu, G., Nishimura, M., Chen, F., Tandon, A., et al. (2000) Mutation of the conserved N-terminal cysteine (Cys92) of human presenilin 1 causes increased Abeta 42 secretion in mammalian cells by impaired Notch/Lin12 signalling in C. elegans embryos. Neuroreport 11, 3227-3230.