Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study.

Published online

Journal Article

Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer's dementia, while the APOE2 allele is associated with a lower risk of Alzheimer's dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer's dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer's dementia cases and controls. APOE2/2 was associated with a low Alzheimer's dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer's disease could have a major impact on the understanding, treatment and prevention of the disease.

Full Text

Duke Authors

Cited Authors

  • Reiman, EM; Arboleda-Velasquez, JF; Quiroz, YT; Huentelman, MJ; Beach, TG; Caselli, RJ; Chen, Y; Su, Y; Myers, AJ; Hardy, J; Paul Vonsattel, J; Younkin, SG; Bennett, DA; De Jager, PL; Larson, EB; Crane, PK; Keene, CD; Kamboh, MI; Kofler, JK; Duque, L; Gilbert, JR; Gwirtsman, HE; Buxbaum, JD; Dickson, DW; Frosch, MP; Ghetti, BF; Lunetta, KL; Wang, L-S; Hyman, BT; Kukull, WA; Foroud, T; Haines, JL; Mayeux, RP; Pericak-Vance, MA; Schneider, JA; Trojanowski, JQ; Farrer, LA; Schellenberg, GD; Beecham, GW; Montine, TJ; Jun, GR; Alzheimer’s Disease Genetics Consortium,

Published Date

  • February 3, 2020

Published In

Volume / Issue

  • 11 / 1

Start / End Page

  • 667 -

PubMed ID

  • 32015339

Pubmed Central ID

  • 32015339

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-019-14279-8


  • eng

Conference Location

  • England