Alzheimer's Disease Genetics Research

APOE4 gene form is discovered as first genetic risk factor for late onset AD

In 1993, scientists reported the landmark discovery that the apolipoprotein () ɛ4 allele on chromosome 19 was a significant risk factor for late-onset Alzheimer’s disease. This finding   substantially advanced the understanding of Alzheimer’s disease by associating the disease with an identifiable genetic risk factor. The discovery of APOE influenced a new direction in research and continues to be foundational to the development of diagnostics and therapies.

REFERENCES

  1. A study published in the Proceedings of the National Academy of Sciences (PNAS) confirmed the association between APOE ɛ4 and Alzheimer’s disease and showed evidence of high avidity binding between APOE and beta-amyloid—the peptide associated with plaques.

Strittmatter, WJ, Saunders, AM, Schmechel, D, Pericak-Vance, M, Enghild, J, Salvesen, GS, & Roses, AD. 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. 1993;90(5)1977–1981. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC46003/

  1. A groundbreaking study published in Nature in 1993 showed that the APOE ɛ4 allele was a significant genetic risk factor associated with late-onset Alzheimer’s disease.

Corder, EH, Saunders, AM, Strittmatter, WJ, Schmechel, DE, Gaskell, PC, Small, GW, Roses, AD, Haines, JL, & Pericak-Vance, MA. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science. 1993;261(5123)921–923. https://doi.org/10.1126/science.8346443

  1. A study published in Neurology expanded on the original study, showing that the APOE ɛ4 allele was associated with both familial and sporadic Alzheimer’s disease.

Saunders AM, Strittmatter WJ, Schmechel D, St. George-Hyslop, PH, Pericak-Vance, MA, Joo, SH, Rosi, BL, Gusella, JF, Crapper-MacLachlan, DR, Alberts, MJ, Hulette, C, Crain, B, Goldgaber, D, Roses, AD. Association of apolipoprotein E allele ε4 with late-onset familial and sporadic Alzheimer’s disease. Neurology. 1993;43(8):1467-1472. https://doi:10.1212/wnl.43.8.1467

  1. Another PNAS study further explored the interaction between APOE and beta-amyloid peptide as a potential mechanism for neuronal loss.

Strittmatter WJ, Weisgraber KH, Huang DY, Dong, LM, Salvesen, GS, Pericak-Vance, M, Schmechel, D, Saunders, AM, Goldgaber, D, and Roses, AD. Binding of human apolipoprotein E to synthetic amyloid β peptide: Isoform-specific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci USA. 1993;90(17):8098-8102. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC47295/