About this Journal Submit a Manuscript Table of Contents
Scientifica
Volume 2012 (2012), Article ID 246210, 14 pages
http://dx.doi.org/10.6064/2012/246210
Review Article

The Genetics of Alzheimer’s Disease

Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107, USA

Received 4 October 2012; Accepted 28 November 2012

Academic Editors: J. A. Castro, Y. Chagnon, J. Gayan, O. Lao, and S. Safieddine

Copyright © 2012 Robert C. Barber. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Strassnig and M. Ganguli, “About a peculiar disease of the cerebral cortex: Alzheimer's original case revisited,” Psychiatry, vol. 2, pp. 30–33, 2005.
  2. D. J. Selkoe, “Biochemistry and molecular biology of amyloid β-protein and the mechanism of Alzheimer's disease,” Handbook of Clinical Neurology, vol. 89, pp. 245–260, 2008. View at Publisher · View at Google Scholar · View at Scopus
  3. D. J. Selkoe, “Alzheimer's disease: a central role for amyloid,” Journal of Neuropathology and Experimental Neurology, vol. 53, no. 5, pp. 438–447, 1994. View at Scopus
  4. H. Braak and E. Braak, “Evolution of neuronal changes in the course of alzheimer's disease,” Journal of Neural Transmission, no. 53, pp. 127–140, 1998. View at Scopus
  5. K. Beyreuther, T. Dyrks, C. Hilbich et al., “Amyloid precursor protein (APP) and beta A4 amyloid in Alzheimer's disease and Down syndrome,” Progress in clinical and biological research, vol. 379, pp. 159–182, 1992. View at Scopus
  6. M. D. Weingarten, A. H. Lockwood, S. Y. Hwo, and M. W. Kirschner, “A protein factor essential for microtubule assembly,” Proceedings of the National Academy of Sciences of the United States of America, vol. 72, no. 5, pp. 1858–1862, 1975. View at Scopus
  7. G. Waldemar, B. Dubois, M. Emre et al., “Recommendations for the diagnosis and management of Alzheimer's disease and other disorders associated with dementia: EFNS guideline,” European Journal of Neurology, vol. 14, no. 1, pp. e1–e26, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. G. L. Wenk, “Neuropathologic changes in Alzheimer's disease,” Journal of Clinical Psychiatry, vol. 64, Supplement 9, pp. 7–10, 2003. View at Scopus
  9. R. S. Desikan, H. J. Cabral, C. P. Hess et al., “Automated MRI measures identify individuals with mild cognitive impairment and Alzheimers disease,” Brain, vol. 132, no. 8, pp. 2048–2057, 2009. View at Publisher · View at Google Scholar · View at Scopus
  10. G. B. Frisoni, N. C. Fox, C. R. Jack Jr., P. Scheltens, and P. M. Thompson, “The clinical use of structural MRI in Alzheimer disease,” Nature Reviews Neurology, vol. 6, no. 2, pp. 67–77, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. Alzheimer's Association, “2012 Alzheimer's disease facts and figures,” Alzheimer's #38; Dementia, vol. 8, pp. 131–168, 2012.
  12. S. F. Lee, S. Shah, H. Li, C. Yu, W. Han, and G. Yu, “Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-β precursor protein and Notch,” Journal of Biological Chemistry, vol. 277, no. 47, pp. 45013–45019, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. R. N. Martins, B. A. Turner, R. T. Carroll et al., “High levels of amyloid-β protein from S182 (Glu246) familial Alzheimer's cells,” NeuroReport, vol. 7, no. 1, pp. 217–220, 1995. View at Scopus
  14. N. Acosta-Baena, D. Sepulveda-Falla, C. M. Lopera-Gómez et al., “Pre-dementia clinical stages in presenilin 1 E280A familial early-onset Alzheimer's disease: a retrospective cohort study,” The Lancet Neurology, vol. 10, no. 3, pp. 213–220, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. R. E. Tanzi, J. F. Gusella, P. C. Watkins, et al., “Amyloid β protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus,” Science, vol. 235, no. 4791, pp. 880–884, 1987. View at Scopus
  16. N. K. Robakis, N. Ramakrishna, G. Wolfe, and H. M. Wisniewski, “Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides,” Proceedings of the National Academy of Sciences of the United States of America, vol. 84, no. 12, pp. 4190–4194, 1987. View at Scopus
  17. J. Hardy, “Amyloid, the presenilins and Alzheimer's disease,” Trends in Neurosciences, vol. 20, no. 4, pp. 154–159, 1997. View at Publisher · View at Google Scholar · View at Scopus
  18. J. W. Lustbader, M. Cirilli, C. Lin et al., “ABAD directly links Aβ to mitochondrial toxicity in Alzheimer's disease,” Science, vol. 304, no. 5669, pp. 448–452, 2004. View at Publisher · View at Google Scholar · View at Scopus
  19. P. H. St George-Hyslop, R. E. Tanzi, R. J. Polinsky, et al., “The genetic defect causing familial Alzheimer's disease maps on chromosome 21,” Science, vol. 235, no. 4791, pp. 885–890, 1987. View at Scopus
  20. P. H. St George-Hyslop, J. L. Haines, L. A. Farrer et al., “Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder,” Nature, vol. 347, no. 6289, pp. 194–197, 1990. View at Publisher · View at Google Scholar · View at Scopus
  21. A. Goate, “Segregation of a missense mutation in the amyloid β-protein precursor gene with familial Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 9, no. 3, pp. 341–347, 2006. View at Scopus
  22. G. D. Schellenberg, T. D. Bird, E. M. Wijsman et al., “Absence of linkage of chromosome 21q21 markers to familial Alzheimer's disease,” Science, vol. 241, no. 4872, pp. 1507–1510, 1988. View at Scopus
  23. R. E. Tanzi, G. Vaula, D. M. Romano et al., “Assessment of amyloid β-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases,” American Journal of Human Genetics, vol. 51, no. 2, pp. 273–282, 1992. View at Scopus
  24. K. Kamino, H. T. Orr, H. Payami et al., “Linkage and mutational analysis of familial Alzheimer disease kindreds for the APP gene region,” American Journal of Human Genetics, vol. 51, no. 5, pp. 998–1014, 1992. View at Scopus
  25. A. Goate, M. C. Chartier-Harlin, M. Mullan et al., “Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease,” Nature, vol. 349, no. 6311, pp. 704–706, 1991. View at Publisher · View at Google Scholar · View at Scopus
  26. G. Raux, L. Guyant-Maréchal, C. Martin et al., “Molecular diagnosis of autosomal dominant early onset Alzheimer's disease: an update,” Journal of Medical Genetics, vol. 42, no. 10, pp. 793–795, 2005. View at Publisher · View at Google Scholar · View at Scopus
  27. N. Suzuki, T. T. Cheung, X. D. Cai et al., “An increased percentage of long amyloid β protein secreted by familial amyloid β protein precursor (βAPP717) mutants,” Science, vol. 264, no. 5163, pp. 1336–1340, 1994. View at Scopus
  28. T. Yamatsuji, T. Matsui, T. Okamoto et al., “G protein-mediated neuronal DNA fragmentation induced by familial Alzheimer's disease-associated mutants of APP,” Science, vol. 272, no. 5266, pp. 1349–1352, 1996. View at Scopus
  29. T. Jonsson, J. K. Atwal, S. Steinberg, et al., “A mutation in APP protects against Alzheimer's disease and age-related cognitive decline,” Nature, vol. 488, pp. 96–99, 2012. View at Publisher · View at Google Scholar
  30. D. Scheuner, C. Eckman, M. Jensen et al., “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,” Nature Medicine, vol. 2, no. 8, pp. 864–870, 1996. View at Publisher · View at Google Scholar · View at Scopus
  31. K. Duff, C. Eckman, C. Zehr et al., “Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1,” Nature, vol. 383, no. 6602, pp. 710–713, 1996. View at Publisher · View at Google Scholar · View at Scopus
  32. M. Citron, D. Westaway, W. Xia et al., “Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice,” Nature Medicine, vol. 3, no. 1, pp. 67–72, 1997. View at Publisher · View at Google Scholar · View at Scopus
  33. P. H. St George-Hyslop and A. Petit, “Molecular biology and genetics of Alzheimer's disease,” Comptes Rendus Biologies, vol. 328, no. 2, pp. 119–130, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. G. L. Boulianne, I. Livne-Bar, J. M. Humphreys et al., “Cloning and characterization of the Drosophila presenilin homologue,” NeuroReport, vol. 8, no. 4, pp. 1025–1029, 1997. View at Scopus
  35. D. Levitan and I. Greenwald, “Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans s182 Alzheimer's disease gene,” Nature, vol. 377, no. 6547, pp. 351–354, 1995. View at Scopus
  36. R. Sherrington, E. I. Rogaev, Y. Liang et al., “Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease,” Nature, vol. 375, no. 6534, pp. 754–760, 1995. View at Scopus
  37. E. I. Rogaev, R. Sherrington, E. A. Rogaeva 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, vol. 376, no. 6543, pp. 775–778, 1995. View at Scopus
  38. A. Herreman, D. Hartmann, W. Annaert et al., “Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 21, pp. 11872–11877, 1999. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. M. Li, M. Xu, M. T. Lai et al., “Photoactivated γ-secretase inhibitors directed to the active site covalently label presenilin 1,” Nature, vol. 405, no. 6787, pp. 689–694, 2000. View at Publisher · View at Google Scholar · View at Scopus
  40. R. Kopan and A. Goate, “A common enzyme connects Notch signaling and Alzheimer's disease,” Genes and Development, vol. 14, no. 22, pp. 2799–2806, 2000. View at Publisher · View at Google Scholar · View at Scopus
  41. D. Cai, W. J. Netzer, M. Zhong et al., “Presenilin-1 uses phospholipase D1 as a negative regulator of β-amyloid formation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 6, pp. 1941–1946, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. D. Cai, M. Zhong, R. Wang et al., “Phospholipase D1 corrects impaired βAPP trafficking and neurite outgrowth in familial Alzheimer's disease-linked presenilin-1 mutant neurons,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 6, pp. 1936–1940, 2006. View at Publisher · View at Google Scholar · View at Scopus
  43. J. A. Davis, S. Naruse, H. Chen et al., “An Alzheimer's disease-linked PS1 variant rescues the developmental abnormalities of PS1-deficient embryos,” Neuron, vol. 20, no. 3, pp. 603–609, 1998. View at Publisher · View at Google Scholar · View at Scopus
  44. S. Qian, P. Jiang, X. M. Guan et al., “Mutant human presenilin 1 protects presenilin 1 null mouse against embryonic lethality and elevates Aβ1-42/43 expression,” Neuron, vol. 20, no. 3, pp. 611–617, 1998. View at Publisher · View at Google Scholar · View at Scopus
  45. S. Sato, K. Kamino, T. Miki et al., “Splicing mutation of presenilin-1 gene for early-onset familial Alzheimer's disease,” Human Mutation, vol. 10, Supplement 1, pp. S91–S94, 1998. View at Scopus
  46. J. Perez-Tur, S. Froelich, G. Prihar et al., “A mutation in Alzheimer's disease destroying a splice acceptor site in the presenilin-1 gene,” NeuroReport, vol. 7, no. 1, pp. 297–301, 1995. View at Scopus
  47. R. Sherrington, S. Froelich, S. Sorbi et al., “Alzheimer's disease associated with mutations in presenilin 2 is rare and variably penetrant,” Human Molecular Genetics, vol. 5, no. 7, pp. 985–988, 1996. View at Publisher · View at Google Scholar · View at Scopus
  48. T. D. Bird, E. Levy-Lahad, P. Poorkaj et al., “Wide range in age of onset for chromosome 1-related familial Alzheimer's disease,” Annals of Neurology, vol. 40, no. 6, pp. 932–936, 1996. View at Publisher · View at Google Scholar · View at Scopus
  49. T. D. Bird, T. H. Lampe, E. J. Nemens, G. W. Miner, S. M. Sumi, and G. D. Schellenberg, “Familial Alzheimer's disease in American descendants of the volga germans: probable genetic founder effect,” Annals of Neurology, vol. 23, no. 1, pp. 25–31, 1988. View at Scopus
  50. T. D. Bird, S. M. Sumi, E. J. Nemens et al., “Phenotypic heterogeneity in familial Alzheimer's disease: a study of 24 kindreds,” Annals of Neurology, vol. 25, no. 1, pp. 12–25, 1989. View at Scopus
  51. M. Gatz, C. A. Reynolds, L. Fratiglioni et al., “Role of genes and environments for explaining Alzheimer disease,” Archives of General Psychiatry, vol. 63, no. 2, pp. 168–174, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. M. A. Pericak-Vance, J. L. Bebout, P. C. Gaskell Jr. et al., “Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage,” American Journal of Human Genetics, vol. 48, no. 6, pp. 1034–1050, 1991. View at Scopus
  53. A. D. Roses and A. M. Saunders, “APOE is a major susceptibility gene for Alzheimer's disease,” Current Opinion in Biotechnology, vol. 5, no. 6, pp. 663–667, 1994. View at Scopus
  54. H. M. Colhoun, P. M. McKeigue, and G. D. Smith, “Problems of reporting genetic associations with complex outcomes,” The Lancet, vol. 361, no. 9360, pp. 865–872, 2003. View at Publisher · View at Google Scholar · View at Scopus
  55. J. P. A. Ioannidis, E. E. Ntzani, T. A. Trikalinos, and D. G. Contopoulos-Ioannidis, “Replication validity of genetic association studies,” Nature Genetics, vol. 29, no. 3, pp. 306–309, 2001. View at Publisher · View at Google Scholar · View at Scopus
  56. J. C. Lambert, S. Heath, G. Even et al., “Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimer's disease,” Nature Genetics, vol. 41, no. 10, pp. 1094–1099, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. D. Harold, R. Abraham, P. Hollingworth et al., “Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease,” Nature Genetics, vol. 41, no. 10, pp. 1088–1093, 2009. View at Publisher · View at Google Scholar · View at Scopus
  58. S. Seshadri, A. L. Fitzpatrick, M. A. Ikram, et al., “Genome-wide analysis of genetic loci associated with Alzheimer disease,” Journal of the American Medical Association, vol. 303, pp. 1832–1840, 2010.
  59. R. Redon, S. Ishikawa, K. R. Fitch et al., “Global variation in copy number in the human genome,” Nature, vol. 444, no. 7118, pp. 444–454, 2006. View at Publisher · View at Google Scholar · View at Scopus
  60. B. E. Stranger, M. S. Forrest, M. Dunning et al., “Relative impact of nucleotide and copy number variation on gene phenotypes,” Science, vol. 315, no. 5813, pp. 848–853, 2007. View at Publisher · View at Google Scholar · View at Scopus
  61. N. Brouwers, C. Van Cauwenberghe, S. Engelborghs et al., “Alzheimer risk associated with a copy number variation in the complement receptor 1 increasing C3b/C4b binding sites,” Molecular Psychiatry, vol. 17, pp. 223–233, 2012. View at Publisher · View at Google Scholar · View at Scopus
  62. R. C. A. Pearson, “Cortical connections and the pathology of Alzheimer's disease,” Neurodegeneration, vol. 5, no. 4, pp. 429–434, 1996. View at Publisher · View at Google Scholar · View at Scopus
  63. P. A. Thomann, V. Dos Santos, U. Seidl, P. Toro, M. Essig, and J. Schröder, “MRI-derived atrophy of the olfactory bulb and tract in mild cognitive impairment and Alzheimer's disease,” Journal of Alzheimer's Disease, vol. 17, no. 1, pp. 213–221, 2009. View at Publisher · View at Google Scholar · View at Scopus
  64. M. H. Tan, K. L. Weldon, J. J. Albers, et al., “Serum HDL-cholesterol, apo-A-I and apo-E levels in patients with abnormal coronary arteries,” Clinical and Investigative Medicine, vol. 3, no. 3-4, pp. 225–232, 1980. View at Scopus
  65. V. I. Zannis and J. L. Breslow, “Apolipoprotein E,” Molecular and Cellular Biochemistry, vol. 42, no. 1, pp. 3–20, 1982. View at Publisher · View at Google Scholar · View at Scopus
  66. J. D. Morrisett, H. S. Kim, and J. R. Patsch, “Genetic susceptibility and resistance to diet-induced atherosclerosis and hyperlipoproteinemia,” Arteriosclerosis, vol. 2, no. 4, pp. 312–324, 1982. View at Scopus
  67. S. C. Rall Jr., K. H. Weisgraber, and R. W. Mahley, “Human apolipoprotein E. The complete amino acid sequence,” Journal of Biological Chemistry, vol. 257, no. 8, pp. 4171–4178, 1982. View at Scopus
  68. K. H. Weisgraber, S. C. Rall Jr., and R. W. Mahley, “Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms,” Journal of Biological Chemistry, vol. 256, no. 17, pp. 9077–9083, 1981. View at Scopus
  69. S. C. Rall Jr., K. H. Weisgraber, T. L. Innerarity, and R. W. Mahley, “Structural basis for receptor binding heterogeneity of apolipoprotein E from type III hyperlipoproteinemic subjects,” Proceedings of the National Academy of Sciences of the United States of America, vol. 79, no. 15, pp. 4696–4700, 1982. View at Scopus
  70. G. Maestre, R. Ottman, Y. Stern et al., “Apolipoprotein E and Alzheimer's disease: ethnic variation in genotypic risks,” Annals of Neurology, vol. 37, no. 2, pp. 254–259, 1995. View at Publisher · View at Google Scholar · View at Scopus
  71. L. A. Farrer, L. A. Cupples, J. L. Haines et al., “Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis,” Journal of the American Medical Association, vol. 278, no. 16, pp. 1349–1356, 1997. View at Scopus
  72. M. N. Haan, D. M. Mungas, H. M. Gonzalez, T. A. Ortiz, A. Acharya, and W. J. Jagust, “Prevalence of dementia in older Latinos: the influence of type 2 diabetes mellitus, stroke and genetic factors,” Journal of the American Geriatrics Society, vol. 51, no. 2, pp. 169–177, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. D. T. A. Eisenberg, C. W. Kuzawa, and M. G. Hayes, “Worldwide allele frequencies of the human apolipoprotein E gene: climate, local adaptations, and evolutionary history,” American Journal of Physical Anthropology, vol. 143, no. 1, pp. 100–111, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. A. M. Saunders, W. J. Strittmatter, D. Schmechel et al., “Association of apolipoprotein E allele ε4 with late-onset familial and sporadic Alzheimer's disease,” Neurology, vol. 43, no. 8, pp. 1467–1472, 1993. View at Scopus
  75. A. D. Roses, “Apolipoprotein E alleles as risk factors in Alzheimer's disease,” Annual Review of Medicine, vol. 47, pp. 387–400, 1996. View at Publisher · View at Google Scholar · View at Scopus
  76. E. H. Corder, A. M. Saunders, W. J. Strittmatter et al., “Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families,” Science, vol. 261, no. 5123, pp. 921–923, 1993. View at Scopus
  77. E. H. Corder, A. M. Saunders, N. J. Risch et al., “Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease,” Nature Genetics, vol. 7, no. 2, pp. 180–184, 1994. View at Publisher · View at Google Scholar · View at Scopus
  78. R. Mayeux, R. Ottman, G. Maestre et al., “Synergistic effects of traumatic head injury and apolipoprotein-ε4 in patients with Alzheimer's disease,” Neurology, vol. 45, no. 3, pp. 555–557, 1995. View at Scopus
  79. M. F. Newman, N. D. Croughwell, J. A. Blumenthal et al., “Predictors of cognitive decline after cardiac operation,” Annals of Thoracic Surgery, vol. 59, no. 5, pp. 1326–1330, 1995. View at Publisher · View at Google Scholar · View at Scopus
  80. M. J. Alberts, C. Graffagnino, C. McClenny et al., “ApoE genotype and survival from intracerebral haemorrhage,” The Lancet, vol. 346, no. 8974, article 575, 1995. View at Scopus
  81. A. C. Naj, G. Jun, G. W. Beecham et al., “Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease,” Nature Genetics, vol. 43, no. 5, pp. 436–441, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. G. Jun, A. C. Naj, G. W. Beecham et al., “Meta-analysis confirms CR1, CLU, and PICALM as Alzheimer disease risk loci and reveals interactions with APOE genotypes,” Archives of Neurology, vol. 67, no. 12, pp. 1473–1484, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. S. E. Jones and C. Jomary, “Clusterin,” International Journal of Biochemistry and Cell Biology, vol. 34, no. 5, pp. 427–431, 2002. View at Publisher · View at Google Scholar · View at Scopus
  84. H. V. De Silva, W. D. Stuart, C. R. Duvic et al., “A 70-kDa apolipoprotein designated ApoJ is a marker for subclasses of human plasma high density lipoproteins,” Journal of Biological Chemistry, vol. 265, no. 22, pp. 13240–13247, 1990. View at Scopus
  85. D. T. Humphreys, J. A. Carver, S. B. Easterbrook-Smith, and M. R. Wilson, “Clusterin has chaperone-like activity similar to that of small heat shock proteins,” Journal of Biological Chemistry, vol. 274, no. 11, pp. 6875–6881, 1999. View at Publisher · View at Google Scholar · View at Scopus
  86. P. Wong, D. Taillefer, J. Lakins, J. Pineault, G. Chader, and M. Tenniswood, “Molecular characterization of human TRPM-2/clusterin, a gene associated with sperm maturation, apoptosis and neurodegeneration,” European Journal of Biochemistry, vol. 221, no. 3, pp. 917–925, 1994. View at Scopus
  87. I. B. Fritz, K. Burdzy, B. Setchell, and O. Blaschuk, “Ram rete testis fluid contains a protein (clusterin) which influences cell-cell interactions in vitro,” Biology of Reproduction, vol. 28, no. 5, pp. 1173–1188, 1983. View at Scopus
  88. M. Calero, A. Rostagno, E. Matsubara, B. Zlokovic, B. Frangione, and J. Ghiso, “Apolipoprotein J (clusterin) and Alzheimer's disease,” Microscopy Research and Technique, vol. 50, pp. 305–315, 2000.
  89. P. Giannakopoulos, E. Kövari, L. E. French, I. Viard, P. R. Hof, and C. Bouras, “Possible neuroprotective role of clusterin in Alzheimer's disease: a quantitative immunocytochemical study,” Acta Neuropathologica, vol. 95, no. 4, pp. 387–394, 1998. View at Publisher · View at Google Scholar · View at Scopus
  90. W. S. Liang, T. Dunckley, T. G. Beach et al., “Altered neuronal gene expression in brain regions differentially affected by Alzheimer's disease: a reference data set,” Physiological Genomics, vol. 33, no. 2, pp. 240–256, 2008. View at Publisher · View at Google Scholar · View at Scopus
  91. P. L. McGeer, T. Kawamata, and D. G. Walker, “Distribution of clusterin in Alzheimer brain tissue,” Brain Research, vol. 579, no. 2, pp. 337–341, 1992. View at Publisher · View at Google Scholar · View at Scopus
  92. M. Calero, A. Rostagno, E. Matsubara, B. Zlokovic, B. Frangione, and J. Ghiso, “Apolipoprotein J (clusterin) and Alzheimer's disease,” Microscopy Research and Technique, vol. 50, pp. 305–315, 2000.
  93. T. Nuutinen, T. Suuronen, A. Kauppinen, and A. Salminen, “Clusterin: a forgotten player in Alzheimer's disease,” Brain Research Reviews, vol. 61, no. 2, pp. 89–104, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. P. C. May, M. Lampert-Etchells, S. A. Johnson, J. Poirier, J. N. Masters, and C. E. Finch, “Dynamics of gene expression for a hippocampal glycoprotein elevated in Alzheimer's disease and in response to experimental lesions in rat,” Neuron, vol. 5, no. 6, pp. 831–839, 1990. View at Publisher · View at Google Scholar · View at Scopus
  95. M. M. Bartl, T. Luckenbach, O. Bergner, O. Ullrich, and C. Koch-Brandt, “Multiple receptors mediate apoJ-dependent clearance of cellular debris into nonprofessional phagocytes,” Experimental Cell Research, vol. 271, no. 1, pp. 130–141, 2001. View at Publisher · View at Google Scholar · View at Scopus
  96. R. D. Bell, A. P. Sagare, A. E. Friedman et al., “Transport pathways for clearance of human Alzheimer's amyloid β-peptide and apolipoproteins E and J in the mouse central nervous system,” Journal of Cerebral Blood Flow and Metabolism, vol. 27, no. 5, pp. 909–918, 2007. View at Publisher · View at Google Scholar · View at Scopus
  97. M. R. Wilson and S. B. Easterbrook-Smith, “Clusterin is a secreted mammalian chaperone,” Trends in Biochemical Sciences, vol. 25, no. 3, pp. 95–98, 2000. View at Publisher · View at Google Scholar · View at Scopus
  98. A. Harel, F. Wu, M. P. Mattson, C. M. Morris, and P. J. Yao, “Evidence for CALM in directing VAMP2 trafficking,” Traffic, vol. 9, no. 3, pp. 417–429, 2008. View at Publisher · View at Google Scholar · View at Scopus
  99. F. Tebar, S. K. Bohlander, and A. Sorkin, “Clathrin assembly lymphoid myeloid leukemia (CALM) protein: localization in endocytic-coated pits, interactions with clathrin, and the impact of overexpression on clathrin-mediated traffic,” Molecular Biology of the Cell, vol. 10, no. 8, pp. 2687–2702, 1999. View at Scopus
  100. S. Pant, M. Sharma, K. Patel, S. Caplan, C. M. Carr, and B. D. Grant, “AMPH-1/Amphiphysin/Bin1 functions with RME-1/Ehd1 in endocytic recycling,” Nature cell biology, vol. 11, no. 12, pp. 1399–1410, 2009. View at Scopus
  101. C. Nordstedt, G. L. Caporaso, J. Thyberg, S. E. Gandy, and P. Greengard, “Identification of the Alzheimer β/A4 amyloid precursor protein in clathrin-coated vesicles purified from PC12 cells,” Journal of Biological Chemistry, vol. 268, no. 1, pp. 608–612, 1993. View at Scopus
  102. M. L. Klebig, M. D. Wall, M. D. Potter, E. L. Rowe, D. A. Carpenter, and E. M. Rinchik, “Mutations in the clathrin-assembly gene Picalm are responsible for the hematopoietic and iron metabolism abnormalities in fit1 mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 14, pp. 8360–8365, 2003. View at Publisher · View at Google Scholar · View at Scopus
  103. L. F. Archangelo, J. Gläsner, A. Krause, and S. K. Bohlander, “The novel CALM interactor CATS influences the subcellular localization of the leukemogenic fusion protein CALM/AF10,” Oncogene, vol. 25, no. 29, pp. 4099–4109, 2006. View at Publisher · View at Google Scholar · View at Scopus
  104. A. Meyerholz, L. Hinrichsen, S. Groos, P. C. Esk, G. Brandes, and E. J. Ungewickell, “Effect of clathrin assembly lymphoid myeloid leukemia protein depletion on clathrin coat formation,” Traffic, vol. 6, no. 12, pp. 1225–1234, 2005. View at Publisher · View at Google Scholar · View at Scopus
  105. M. H. Dreyling, J. A. Martinez-Climent, M. Zheng, J. Mao, J. D. Rowley, and S. K. Bohlander, “The t(10;11)(p13;q14) in the U937 cell line results in the fusion of the AF10 gene and CALM, encoding a new member of the AP-3 clathrin assembly protein family,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 10, pp. 4804–4809, 1996. View at Publisher · View at Google Scholar · View at Scopus
  106. J. G. Wilson, N. A. Andriopoulos, and D. T. Fearon, “CR1 and the cell membrane proteins that bind C3 and C4. A basic and clinical review,” Immunologic Research, vol. 6, no. 3, pp. 192–209, 1987. View at Scopus
  107. D. T. Fearon and W. W. Wong, “Complement ligand-receptor interactions that mediate biological responses,” Annual Review of Immunology, vol. 1, pp. 243–271, 1983. View at Scopus
  108. S. Minota, C. Terai, and Y. Nojima, “Low C3b receptor reactivity on erythrocytes from patients with systemic lupus erythematosus detected by immune adherence hemagglutination and radioimmunoassays with monoclonal antibody,” Arthritis and Rheumatism, vol. 27, no. 12, pp. 1329–1335, 1984. View at Scopus
  109. K. Iida, R. Mornaghi, and V. Nussenzweig, “Complement receptor (CR1) deficiency in erythrocytes from patients with systemic lupus erythematosus,” Journal of Experimental Medicine, vol. 155, no. 5, pp. 1427–1438, 1982. View at Scopus
  110. J. H. Weis, C. C. Morton, and G. A. P. Bruns, “A complement receptor locus: genes encoding C3b/C4b receptor and C3d/Epstein-Barr virus receptor map to 1q32,” Journal of Immunology, vol. 138, no. 1, pp. 312–315, 1987. View at Scopus
  111. J. M. Moulds, M. W. Nickells, J. J. Moulds, M. C. Brown, and J. P. Atkinson, “The C3b/C4b receptor is recognized by the Knops, McCoy, Swain-Langley, and York blood group antisera,” Journal of Experimental Medicine, vol. 173, no. 5, pp. 1159–1163, 1991. View at Scopus
  112. W. W. Wong, J. M. Cahill, M. D. Rosen et al., “Structure of the human CR1 gene. Molecular basis of the structural and quantitative polymorphisms and identification of a new CR1-like allele,” Journal of Experimental Medicine, vol. 169, no. 3, pp. 847–863, 1989. View at Scopus
  113. D. Sakamuro, K. J. Elliott, R. Wechsler-Reya, and G. C. Prendergast, “BIN1 is a novel MYC-interacting protein with features of a tumour suppressor,” Nature Genetics, vol. 14, no. 1, pp. 69–77, 1996. View at Publisher · View at Google Scholar · View at Scopus
  114. A. S. Nicot, A. Toussaint, V. Tosch et al., “Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy,” Nature Genetics, vol. 39, no. 9, pp. 1134–1139, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. W. E. Kaminski, E. Orsó, W. Diederich, J. Klucken, W. Drobnik, and G. Schmitz, “Identification of a novel human sterol-sensitive ATP-binding cassette transporter (ABCA7),” Biochemical and Biophysical Research Communications, vol. 273, no. 2, pp. 532–538, 2000. View at Publisher · View at Google Scholar · View at Scopus
  116. C. Broccardo, J. Osorio, M. F. Luciani et al., “Comparative analysis of the promoter structure and genomic organization of the human and mouse ABCA7 gene encoding a novel ABCA transporter,” Cytogenetics and Cell Genetics, vol. 92, no. 3-4, pp. 264–270, 2001. View at Scopus
  117. C. Antúnez, M. Boada, A. González-Pérez et al., “The membrane-spanning 4-domains, subfamily A (MS4A) gene cluster contains a common variant associated with Alzheimer's disease,” Genome Medicine, vol. 3, no. 5, article 33, 2011. View at Publisher · View at Google Scholar · View at Scopus
  118. K. Ishibashi, M. Suzuki, S. Sasaki, and M. Imai, “Identification of a new multigene four-transmembrane family (MS4A) related to CD20, HTm4 and β subunit of the high-affinity IgE receptor,” Gene, vol. 264, no. 1, pp. 87–93, 2001. View at Publisher · View at Google Scholar · View at Scopus
  119. Y. Liang, T. R. Buckley, L. Tu, S. D. Langdon, and T. F. Tedder, “Structural organization of the human MS4A gene cluster on Chromosome 11q12,” Immunogenetics, vol. 53, no. 5, pp. 357–368, 2001. View at Publisher · View at Google Scholar · View at Scopus
  120. Y. Liang and T. F. Tedder, “Identification of a CD20-, FcεRIβ-, and HTm4-related gene family: sixteen new MS4A family members expressed in human and mouse,” Genomics, vol. 72, no. 2, pp. 119–127, 2001. View at Publisher · View at Google Scholar · View at Scopus
  121. M. G. Coulthard, J. D. Lickliter, N. Subanesan et al., “Characterization of the EphA1 receptor tyrosine kinase: expression in epithelial tissues,” Growth Factors, vol. 18, no. 4, pp. 303–317, 2001. View at Scopus
  122. R. Zhou, “The Eph family receptors and ligands,” Pharmacology and Therapeutics, vol. 77, no. 3, pp. 151–181, 1998. View at Publisher · View at Google Scholar · View at Scopus
  123. D. G. Wilkinson, “Eph receptors and ephrins: regulators of guidance and assembly,” International Review of Cytology, vol. 196, pp. 177–244, 2000. View at Scopus
  124. Q. Xu, G. Mellitzer, and D. G. Wilkinson, “Roles of Eph receptors and ephrins in segmental patterning,” Philosophical transactions of the Royal Society of London B, vol. 355, no. 1399, pp. 993–1002, 2000. View at Scopus
  125. N. Holder and R. Klein, “Eph receptors and ephrins: effectors of morphogenesis,” Development, vol. 126, no. 10, pp. 2033–2044, 1999. View at Scopus
  126. K. Kullander and R. Klein, “Mechanisms and functions of Eph and ephrin signalling,” Nature Reviews Molecular Cell Biology, vol. 3, no. 7, pp. 475–486, 2002. View at Publisher · View at Google Scholar · View at Scopus
  127. D. Owshalimpur and M. J. Kelley, “Genomic structure of the EPHA1 receptor tyrosine kinase gene,” Molecular and Cellular Probes, vol. 13, no. 3, pp. 169–173, 1999. View at Publisher · View at Google Scholar · View at Scopus
  128. H. Cao and P. R. Crocker, “Evolution of CD33-related siglecs: regulating host immune functions and escaping pathogen exploitation?” Immunology, vol. 132, no. 1, pp. 18–26, 2011. View at Publisher · View at Google Scholar · View at Scopus
  129. P. R. Crocker, J. C. Paulson, and A. Varki, “Siglecs and their roles in the immune system,” Nature Reviews Immunology, vol. 7, no. 4, pp. 255–266, 2007. View at Publisher · View at Google Scholar · View at Scopus
  130. P. R. Crocker and A. Varki, “Siglecs, sialic acids and innate immunity,” Trends in Immunology, vol. 22, no. 6, pp. 337–342, 2001. View at Publisher · View at Google Scholar · View at Scopus
  131. T. Ulyanova, J. Blasioli, T. A. Woodford-Thomas, and M. L. Thomas, “The sialoadhesin CD33 is a myeloid-specific inhibitory receptor,” European Journal of Immunology, vol. 29, pp. 3440–3449, 1999.
  132. S. D. Freeman, S. Kelm, E. K. Barber, and P. R. Crocker, “Characterization of CD33 as a new member of the Sialoadhesin family of cellular interaction molecules,” Blood, vol. 85, no. 8, pp. 2005–2012, 1995. View at Scopus
  133. V. C. Taylor, C. D. Buckley, M. Douglas, A. J. Cody, D. L. Simmons, and S. D. Freeman, “The myeloid-specific sialic acid-binding receptor, CD33, associates with the protein-tyrosine phosphatases, SHP-1 and SHP-2,” Journal of Biological Chemistry, vol. 274, no. 17, pp. 11505–11512, 1999. View at Publisher · View at Google Scholar · View at Scopus
  134. G. M. Yousef, M. H. Ordon, G. Foussias, and E. P. Diamandis, “Genomic organization of the siglec gene locus on chromosome 19q13.4 and cloning of two new siglec pseudogenes,” Gene, vol. 286, no. 2, pp. 259–270, 2002. View at Publisher · View at Google Scholar · View at Scopus
  135. T. Hernández-Caselles, M. Martínez-Esparza, A. B. Pérez-Oliva et al., “A study of CD33 (SIGLEC-3) antigen expression and function on activated human T and NK cells: two isoforms of CD33 are generated by alternative splicing,” Journal of Leukocyte Biology, vol. 79, no. 1, pp. 46–58, 2006. View at Publisher · View at Google Scholar · View at Scopus
  136. D. Simmons and B. Seed, “Isolation of a cDNA encoding CD33, a differentiation antigen of myeloid progenitor cells,” Journal of Immunology, vol. 141, no. 8, pp. 2797–2800, 1988. View at Scopus
  137. K. H. Kirsch, M. M. Georgescu, S. Ishimaru, and H. Hanafusa, “CMS: an adapter molecule involved in cytoskeletal rearrangements,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 11, pp. 6211–6216, 1999. View at Publisher · View at Google Scholar · View at Scopus
  138. M. L. Dustin, M. W. Olszowy, A. D. Holdorf et al., “A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts,” Cell, vol. 94, no. 5, pp. 667–677, 1998. View at Publisher · View at Google Scholar · View at Scopus
  139. J. H. Kim, H. Wu, G. Green et al., “CD2-associated protein haploinsufficiency is linked to glomerular disease susceptibility,” Science, vol. 300, no. 5623, pp. 1298–1300, 2003. View at Publisher · View at Google Scholar · View at Scopus
  140. E. Rogaeva, Y. Meng, J. H. Lee et al., “The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease,” Nature Genetics, vol. 39, no. 2, pp. 168–177, 2007. View at Publisher · View at Google Scholar · View at Scopus
  141. O. M. Andersen, J. Reiche, V. Schmidt et al., “Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 38, pp. 13461–13466, 2005. View at Publisher · View at Google Scholar · View at Scopus
  142. L. Jacobsen, P. Madsen, S. K. Moestrup et al., “Molecular characterization of a novel human hybrid-type receptor that binds the α2-macroglobulin receptor-associated protein,” Journal of Biological Chemistry, vol. 271, no. 49, pp. 31379–31383, 1996. View at Publisher · View at Google Scholar · View at Scopus
  143. C. Reitz, R. Cheng, E. Rogaeva et al., “Meta-analysis of the association between variants in SORL1 and Alzheimer disease,” Archives of Neurology, vol. 68, no. 1, pp. 99–106, 2011. View at Publisher · View at Google Scholar · View at Scopus
  144. K. T. Cuenco, K. L. Lunetta, C. T. Baldwin et al., “Association of distinct variants in SORL1 with cerebrovascular and neurodegenerative changes related to Alzheimer disease,” Archives of Neurology, vol. 65, no. 12, pp. 1640–1648, 2008. View at Publisher · View at Google Scholar · View at Scopus
  145. H. Kölsch, F. Jessen, J. Wiltfang et al., “Influence of SORL1 gene variants: association with CSF amyloid-β products in probable Alzheimer's disease,” Neuroscience Letters, vol. 440, no. 1, pp. 68–71, 2008. View at Publisher · View at Google Scholar · View at Scopus
  146. A. Subramanian, P. Tamayo, V. K. Mootha et al., “Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 43, pp. 15545–15550, 2005. View at Publisher · View at Google Scholar · View at Scopus
  147. A. Torkamani, E. J. Topol, and N. J. Schork, “Pathway analysis of seven common diseases assessed by genome-wide association,” Genomics, vol. 92, no. 5, pp. 265–272, 2008. View at Publisher · View at Google Scholar · View at Scopus
  148. J. C. Lambert, B. Grenier-Boley, V. Chouraki et al., “Implication of the immune system in Alzheimer's disease: evidence from genome-wide pathway analysis,” Journal of Alzheimer's Disease, vol. 20, no. 4, pp. 1107–1118, 2010. View at Publisher · View at Google Scholar · View at Scopus
  149. M. G. Hong, A. Alexeyenko, J. C. Lambert, P. Amouyel, and J. A. Prince, “Genome-wide pathway analysis implicates intracellular transmembrane protein transport in Alzheimer disease,” Journal of Human Genetics, vol. 55, no. 10, pp. 707–709, 2010. View at Publisher · View at Google Scholar · View at Scopus
  150. J. Deelen, M. Beekman, H. W. Uh et al., “Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited,” Aging Cell, vol. 10, no. 4, pp. 686–698, 2011. View at Publisher · View at Google Scholar · View at Scopus
  151. L. M. Bekris, S. P. Millard, N. M. Galloway et al., “Multiple SNPs within and surrounding the apolipoprotein E gene influence cerebrospinal fluid apolipoprotein E protein levels,” Journal of Alzheimer's Disease, vol. 13, no. 3, pp. 255–266, 2008. View at Scopus
  152. L. M. Bekris, N. M. Galloway, T. J. Montine, G. D. Schellenberg, and C. E. Yu, “APOE mRNA and protein expression in postmortem brain are modulated by an extended haplotype structure,” American Journal of Medical Genetics B, vol. 153, no. 2, pp. 409–417, 2010. View at Publisher · View at Google Scholar · View at Scopus
  153. A. D. Roses, “An inherited variable poly-T repeat genotype in TOMM40 in Alzheimer disease,” Archives of Neurology, vol. 67, no. 5, pp. 536–541, 2010. View at Publisher · View at Google Scholar · View at Scopus
  154. A. D. Roses, M. W. Lutz, H. Amrine-Madsen et al., “A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's disease,” Pharmacogenomics Journal, vol. 10, no. 5, pp. 375–384, 2010. View at Publisher · View at Google Scholar · View at Scopus
  155. G. Jun, B. N. Vardarajan, J. Buros, et al., “Comprehensive search for Alzheimer disease susceptibility loci in the APOE region,” Archives of Neurology, vol. 69, no. 10, pp. 1270–1279, 2012. View at Publisher · View at Google Scholar
  156. C. E. Yu, H. Seltman, E. R. Peskind et al., “Comprehensive analysis of APOE and selected proximate markers for late-onset Alzheimer's disease: patterns of linkage disequilibrium and disease/marker association,” Genomics, vol. 89, no. 6, pp. 655–665, 2007. View at Publisher · View at Google Scholar · View at Scopus
  157. V. K. Ramanan, S. Kim, K. Holohan, et al., “Genome-wide pathway analysis of memory impairment in the Alzheimer's disease neuroimaging initiative (ADNI) cohort implicates gene candidatescanonical pathways, and networks,” Brain Imaging and Behavior. In press. View at Publisher · View at Google Scholar
  158. R. Cacabelos, R. Martinez, L. Fernandez-Novoa, et al., “Genomics of dementia: APOE- and CYP2D6-related pharmacogenetics,” International Journal of Alzheimer's Disease, vol. 2012, Article ID 518901, 37 pages, 2012. View at Publisher · View at Google Scholar
  159. R. Cacabelos, R. Llovo, C. Fraile, and L. Fernández-Novoa, “Pharmacogenetic aspects of therapy with cholinesterase inhibitors: the role of CYP2D6 in Alzheimer's disease pharmacogenetics,” Current Alzheimer Research, vol. 4, no. 4, pp. 479–500, 2007. View at Publisher · View at Google Scholar · View at Scopus
  160. R. Cacabelos, “Pharmacogenomics and therapeutic strategies for dementia,” Expert Review of Molecular Diagnostics, vol. 9, no. 6, pp. 567–611, 2009. View at Publisher · View at Google Scholar · View at Scopus
  161. R. Cacabelos, “Pharmacogenetic basis for therapeutic optimization in Alzheimer's disease,” Molecular Diagnosis and Therapy, vol. 11, no. 6, pp. 385–405, 2007. View at Scopus
  162. R. Cacabelos, R. Martinez-Bouza, J. C. Carril, et al., “Genomics and pharmacogenomics of brain disorders,” Current Pharmaceutical Biotechnology, vol. 13, pp. 674–725, 2012. View at Publisher · View at Google Scholar