Skip to main navigation menu Skip to main content Skip to site footer

Narrative Review

Vol. 3 No. 2 (1997)

The Presenilins and Alzheimer Disease

  • G. Lévesque, Ph.D.
  • P. St George-Hyslop, M.D., F.R.C.P.(C).
November 6, 2020




  1. Kertesz A, Mobs RC. In: Gauthier S, ed. Clinical Diagnosis and Management of Alzheimer’s Disease. Martin Dunitz; 1996.
  2. St George-Hyslop P. Genetic of Alzheimer Disease. In: Markesbery W. ed. Neuropathology of dementing diseases. London, Edward Arnold Publishers; 1997.
  3. Foncin JF, Salmon D, Supino-Verbo V, et al. Alzheimer’s presenile dementia transmitted in an extended kindred. Revue Neurologique (Paris) 141(3):194-202; 1985.
  4. Goudsmit J, White BJ, Weitkamp LR, et al. Familial Alzheimer’s disease in two kindreds of the same geographic and ethnic origin: a clinical and genetic study. Journal of Neurological Sciences 49(1): 78-89; 1981.
  5. Katzman R, Kawas CH. The Epidemiology of Dementia and Alzheimer Disease. In: Terry RD, Katzman R, Bick KL, eds. Alzheimer Disease. New York, NY: Raven Press; 1994.
  6. Roses AD. Apolipoprotein E alleles as risk factors in Alzheimer’s disease. Annual Review of Medicine 47:387-400; 1996.
  7. Lambert JC, Perez-Tur J, Dupire MJ, et al. Distortion of allelic expression of apolipoprotein E in Alzheimer’s disease. Human Molecular Genetics 6(12): 2151-2154; 1997.
  8. Farrer LA, Myers RH, Cupples LA, St George-Hyslop PH, Bird TD, Rossor MN. Transmission and age-at-onset patterns in familial Alzheimer’s disease: Evidence for heterogeneity. Neurology 40(3 pt 1): 395-403; 1990.
  9. Schellenberg GD, Bird TD, Wijsman EM, et al Genetic linkage evidence for a familial Alzheimer’s disease locus on chromosome 14. Science 258(5082): 668-671; 1992.
  10. St George-Hyslop P, Haines J, et al. Genetic evidence for a novel familial Alzheimer’s disease locus on chromosome 14. Nature Genetics 2(4): 330-334; 1992.
  11. Van Broeckhoven C, Backhovens H, Cruts M, et al. Mapping of a gene predisposing to early-onset Alzheimer’s disease to chromosome 14q24.3. Nature Genetics 2(4): 335-339; 1992.
  12. Sherrington R, Rogaev EI, Liang Y, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s Disease. Nature 375(6534): 754-760; 1995.
  13. Rogaev EI, Sherrington R, Rogaeva EA, 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(6543): 775-778; 1995.
  14. Levitan D, Greenwald I. Facilitation of lin-12 mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer’s disease gene. Nature 377(6547): 351-354; 1995.
  15. Boulianne GL, Livne-Bar I, Humphreys JM, et al. Cloning and characterization of the Drosophila presenilin homologue. Neuroreport 8(4): 1025-1029; 1997.
  16. Rogaev EI, Sherrington R, Wu C, et al. Analysis of the 5’ sequence, genomic structure, and alternative splicing of the presenilin-1 gene (PSEN1) associated with early onset Alzheimer disease. Genomics 40(3): 415-424; 1997.
  17. The Alzheimer’s disease Collaborative Group: The structure of presenilin 1(S182) gene and the identification of six novel mutations in early onset AD families. Nature Genetics 11(2): 219-222; 1995.
  18. Lehmann S, Chiesa R, Harris DA. Evidence for six transmembrane domain structure of presenilin 1. Journal of Biological. Chemistry 272(18): 12047-12051; 1997.
  19. Doan A, Thinakaran G, Borchelt G, et al. Protein topology of presenilin 1. Neuron 17(5): 1023-1030; 1996.
  20. Levy-Lahad E, Poorkaj P, Wang K, et al. Genomic structure and expression of STM2, the chromosome 1 familial Alzheimer disease gene. Genomics 34(2):198-204; 1996.
  21. Sherrington R, Froelich S, Sorbi S, et al. Alzheimer’s disease associated with mutations in presenilin 2 is rare and variably penetrant. Human Molecular Genetics 5(7): 985-988; 1996.
  22. Perez-Tur J, Froelich S, Prihar G, et al. A mutation in Alzheimer’s disease destroying a splice acceptor site in the presenilin-1 gene. Neuroreport 7(1): 297-301; 1995.
  23. Van Broeckhoven C. Presenilins and Alzheimer disease. Nature Genetics 11(3): 230-232; 1995.
  24. Hutton M, Hardy J. The presenilins and Alzheimer’s disease. Human Molecular Genetics 6(10): 1639-1646; 1997.
  25. St George-Hyslop PH, Lévesque G, Lévesque L, et al. Two homologous genes causing early-onset familial Alzheimer’s disease. Cold Spring Harbor Symposia on Quantitative Biology Vol. LXI: 559-564; 1996.
  26. Thinakaran G, Borchelt DR, Lee MK, et al. Endoproteolysis of presenilin 1 and accumulation of processed derivatives in vivo. Neuron 17(1): 181-190; 1996.
  27. Kim TW, Pettingell WH, Hallmark OG, et al. Endoproteolytic cleavage and proteasomal degradation of presenilin 2 in transfected cells Journal of Biological Chemistry 272(17):11006-11010; 1997.
  28. Podlisny MB, Citron M, Amarante P, et al. Presenilin proteins undergo heterogeneous endoproteolysis between Thr291 and Ala299 and occur as stable N- and C- terminal fragments in normal and Alzheimer brain tissue. Neurobiology of Disease 3(4): 325-337; 1997.
  29. Thinakaran G, Harris CL, Ratovitski T, et al. Evidence that levels of presenilins (PS1 and PS2) are coordinately regulatedby competition for limiting cellular factors. Journal of Biological Chemistry 272: 28415-28422; 1997.
  30. Kovacs DM, Fausett HJ, Page KJ, et al. Alzheimer-associated presenilins 1 and 2: Neuronal expression in brain andlocalization to intracellular membranes in mammalian cells. Nature Medicine 2(2): 224-229; 1996.
  31. Lah JJ, Heilman CJ, Nash NR, et al. Light and electron microscopic localization of presenilin 1 in the primate brain. Journal of Neuroscience. 17(6): 1971-1980; 1997.
  32. De Strooper B, Beullen M, Contreras B, et al. Phosphorylation, subcellular localization, and membrane orientation of the Alzheimer’s disease-associated presenilins. Journal of Biological Chemistry 272(6): 3590-3598; 1997.
  33. Walter J, Capell A, Grunberg J, et al. The Alzheimer’s disease associated presenilins are differentially phosphorylated proteins located predominantly within the endoplasmic reticulum. Molecular. Medicine. 2(6): 673-691; 1996.
  34. Li J, Xu M, Zhou H, Ma J, Potter H. Alzheimer presenilins in the nuclear membrane, interphase kinetochores, and centrosomes suggest a role in chromosome segregation. Cell 90(5): 917-927; 1997.
  35. Wong PC, Zheng H, Chen H, et al. Presenilin 1 is required for Notch 1 and DII 1 expression in the paraxial mesoderm. Nature 387(6630): 288-292; 1997.
  36. Shen J, Bronson RT, Chen DF, Xia W, Selkoe DJ, Tonegawa S. Skeletal and CNS defects in presenilin-1 deficient mice. Cell 89(4): 629-639; 1997.
  37. L’Hernault SW, Arduengo PM. Mutation of a putative sperm membrane protein in Caenorhabditis elegans prevents sperm differentiation but not its associated meiotic divisions. Journal of Cellular Biology 119(1): 55-68; 1992.
  38. Baumeister R, Leimer U, Zweckbronner I, Constanze J, Grunberg J, Haass C. Human presenilin-1, but not familial Alzheimer’s disease (FAD) mutants, facilitate Caenorhabditis elegans Notch signalling independently of proteolytic processing. Genes Function 1: 149-159; 1997.
  39. Conlon RA, Reaume AG, Rossant J. Notch 1 is required for the coordinate segmentation of somites. Development 121(5): 1533-1545; 1995.
  40. Selkoe DJ. Amyloid beta-protein and the genetics of Alzheimer’s disease. Journal of Biological Chemistry 271(31): 18295-18298; 1996.
  41. Scheuner D, Eckman C, Jensen M, et al. Secreted amyloid betaprotein 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 2(8): 864-870; 1996.
  42. Citron M, Westaway D, Weiming X, et al. Mutant Presenilins of Alzheimer's disease increase production of 42-residue amyloid ß-protein in both transfected cells and transgenic mice. Nature Medicine 3(1): 67-72; 1997.
  43. DeStrooper B, Saftig P, Craessaerts K, et al. Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391(6665): 387-390; 1998.
  44. Haas C., Selkoe D.J. A technical KO of amyloid-B peptide. Nature 391(6665): 339-340; 1998.
  45. Duff K, Eckman C, Zehr C, et al. Increase amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature 383(6602): 710-713; 1996.
  46. Kerr JFR, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. British Journal of Cancer 26(4): 239-257; 1972.
  47. Wolozin B, Iwasaki K, Vito P, et al. Participation of presenilin2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation. Science 274(5293): 1710-1713; 1996.
  48. Vito P, Lacana E, D’Adamio L. Interfering with apoptosis: Ca(2+)-binding protein ALG-2 and Alzheimer’s disease gene ALG-3. Science 271(5248): 521-525; 1996.
  49. Lacana E, Ganjei JK, VitoP, D’Adamio L. Dissociation of apoptosis and activation of IL-1ß-converting enzyme/Ced-3 proteases by ALG-2 and the truncated Alzheimer’s disease gene ALG-3. J. Immunology 158(11): 5129-5135; 1997.
  50. Kim TW, Petingell WH, Jung YK, Kovacs DM, Tanzi RE. Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease. Science 277: 373-376; 1997.
  51. Vito P, Ghayur T, D’Adamio L. Generation of anti-apoptotic presenilin-2 polypeptides by alternative transcription, proteolysis, and caspase-3 cleavage. Journal Biological Chemistry 272: 28315-28320; 1997.
  52. Lévesque G, Yu G, St George-Hyslop PH. Genetics of Alzheimer disease. Current Neurology 17: 137-156; 1997.


Download data is not yet available.