biostudies-literatureReiman EMRosetrees TrustNCATS NIH HHSNIA NIH HHSU.S. Department of Health & Human Services | NIH | National Institute on AgingAlzheimers Research UKMedical Research CouncilParkinson's UK667https://www.ebi.ac.uk/biostudies/studies/S-EPMC6997393biostudies-literatureUnknown11(1)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 contNature communicationsExceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study.PMC6997393R01 AG015819ART-PG2010-1ARUK-EG2014A-1R01 AG030653P30 AG010133P01 AG019724M733U01 AG046139P30 AG062715ART-PPG2009A-1MR/N026004/1ARUK-PhD2014-16P30 AG066462RF1 AG057902RF1 AG054023P30 AG019610R01 AG064877U01 AG058922P50 AG008702RF1 AG015473P30 AG010124P30 AG062421P50 AG005136MR/L501542/1P30 AG010161RF1 AG051504UL1 TR002369G0701075P30 AG062429G-0907UKDRI-1009ART-PPG2011A-14R01 AG061796U01 AG032984U24 AG056270R01 AG017917G0901254RF1AG057519, P30-AG10161, R01AG15819, R01AG17917Peskind EO'Bryant SKauwe JSKCarrasquillo MMLunetta KLCarney RMRosen HJMcKee ACPierce ABowen JDDeCarli CSu YJin LWLarson EBRogaeva ERosenberg RNStern RADuara RMartiniuk FKramer JHYounkin SGSano MSchneider JAWu CKBoxer ALah JJGalasko DRSeeley WWPotter HYu LVan Deerlin VMCao CSmith AGZhao YKatz MJReisch JSTsuang DWTanzi REJarvik GPBoeve BFAsthana SGrowdon JHWeintraub SAlbert MSCantwell LBBarber RCBurns JMKunkle BWMalamon JMesulam MBeach TGWoltjer RLKeene CDHuentelman MJApostolova LGKowall NWKuzma APTrojanowski JQReitz CSwerdlow RHKukull WACaselli RJEvans DACrocco EAChen YReisberg BGreen RCRingman JMReiman EMLaFerla FMLi GCrane PKWang LSForoud TBecker JTCarlsson CMPetersen RCBeecham GWAbner EHakonarson HLyketsos CGCribbs DHFardo DWBarral SVan Eldik LJFallon KBMiller BLBigio EHKaye JAArboleda-Velasquez JFPaulson HLPaul Vonsattel JBuxbaum JDMcCurry SMMiller CAHonig LSBaldwin CTGoate AMYu CEDe Jager PLSaykin AJFaber KMHarrell LEQuinn JFKofler JKLipton RBWelsh-Bohmer KAChui HCHyman BTGilbert JRHuebinger RMLieberman APMartin ERSager MASchellenberg GDSpina SPericak-Vance MAValladares OBlacker DKarydas AGhisays VMasliah EVardarajan BNRoyall DRJun GRHulette CMBurke JRWilhelmsen KCAdams PMCruchaga CAtwood CSHamilton-Nelson KLMukherjee SCairns NJDick MNaj ACRoberson EDQu LMcDonough SSonnen JABeekly DMarson DCKim RBennett DAKamboh MIArnold SEHamilton RLAlbin RLDickson DWFairchild TJFarlow MRVinters HVLopez OLOlichney JMGraff-Radford NRMyers AJGhetti BFGeorge-Hyslop PSFarrer LAMcCormick WCWright CBDuque LMayeux RPPoon WWMash DCErtekin-Taner NBarnes LLHardy JMcDavid ANMiller JWHaines JLDoody RSGwirtsman HEGearing MParisi JETroncoso JCFerris SLeverenz JBAlzheimer’s Disease Genetics ConsortiumFrosch MPGeschwind DHWilliamson JSchneider LSLevey AIBird TDRaj AMorris JCCarlson CSWingo TSQuiroz YTLeung YYMontine TJRaskind MfalseExceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study.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 cont2020-01-01T00:00:00Z2020 Feb2025-04-04T22:29:53.931Z2020-05-22T09:35:42ZS-EPMC69973933201533910.1038/s41467-019-14279-8