Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study.
Aged
Aged, 80 and over
Alleles
Alzheimer Disease
/ genetics
Apolipoprotein E2
/ genetics
Apolipoprotein E3
/ genetics
Apolipoprotein E4
/ genetics
Brain
/ metabolism
Female
Genetic Association Studies
Genetic Predisposition to Disease
/ genetics
Genotype
Homozygote
Humans
Male
Middle Aged
Neuropathology
Probability
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
03 02 2020
03 02 2020
Historique:
received:
01
10
2019
accepted:
19
12
2019
entrez:
5
2
2020
pubmed:
6
2
2020
medline:
24
4
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32015339
doi: 10.1038/s41467-019-14279-8
pii: 10.1038/s41467-019-14279-8
pmc: PMC6997393
doi:
Substances chimiques
Apolipoprotein E2
0
Apolipoprotein E3
0
Apolipoprotein E4
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
667Subventions
Organisme : NIA NIH HHS
ID : U01 AG032984
Pays : United States
Organisme : Parkinson's UK
ID : G-0907
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061796
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG046139
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG030653
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : Medical Research Council
ID : G0701075
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0901254
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : R01 AG064877
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010124
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG058922
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010133
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG021886
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062421
Pays : United States
Organisme : Medical Research Council
ID : MR/L501542/1
Pays : United Kingdom
Organisme : NCATS NIH HHS
ID : UL1 TR002369
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG008702
Pays : United States
Organisme : NIA NIH HHS
ID : U24 AG056270
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062429
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG054023
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005136
Pays : United States
Organisme : Medical Research Council
ID : MR/N026004/1
Pays : United Kingdom
Organisme : NIA NIH HHS
ID : RF1 AG051504
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG019724
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066462
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062715
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG015473
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG057902
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG015819
Pays : United States
Investigateurs
Erin Abner
(E)
Perrie M Adams
(PM)
Marilyn S Albert
(MS)
Roger L Albin
(RL)
Liana G Apostolova
(LG)
Steven E Arnold
(SE)
Sanjay Asthana
(S)
Craig S Atwood
(CS)
Clinton T Baldwin
(CT)
Robert C Barber
(RC)
Lisa L Barnes
(LL)
Sandra Barral
(S)
James T Becker
(JT)
Duane Beekly
(D)
Eileen H Bigio
(EH)
Thomas D Bird
(TD)
Deborah Blacker
(D)
Bradley F Boeve
(BF)
James D Bowen
(JD)
Adam Boxer
(A)
James R Burke
(JR)
Jeffrey M Burns
(JM)
Nigel J Cairns
(NJ)
Laura B Cantwell
(LB)
Chuanhai Cao
(C)
Chris S Carlson
(CS)
Cynthia M Carlsson
(CM)
Regina M Carney
(RM)
Minerva M Carrasquillo
(MM)
Helena C Chui
(HC)
David H Cribbs
(DH)
Elizabeth A Crocco
(EA)
Carlos Cruchaga
(C)
Charles DeCarli
(C)
Malcolm Dick
(M)
Rachelle S Doody
(RS)
Ranjan Duara
(R)
Nilufer Ertekin-Taner
(N)
Denis A Evans
(DA)
Kelley M Faber
(KM)
Thomas J Fairchild
(TJ)
Kenneth B Fallon
(KB)
David W Fardo
(DW)
Martin R Farlow
(MR)
Steven Ferris
(S)
Douglas R Galasko
(DR)
Marla Gearing
(M)
Daniel H Geschwind
(DH)
Valentina Ghisays
(V)
Alison M Goate
(AM)
Neill R Graff-Radford
(NR)
Robert C Green
(RC)
John H Growdon
(JH)
Hakon Hakonarson
(H)
Ronald L Hamilton
(RL)
Kara L Hamilton-Nelson
(KL)
Lindy E Harrell
(LE)
Lawrence S Honig
(LS)
Ryan M Huebinger
(RM)
Christine M Hulette
(CM)
Gail P Jarvik
(GP)
Lee-Way Jin
(LW)
Anna Karydas
(A)
Mindy J Katz
(MJ)
John S K Kauwe
(JSK)
Jeffrey A Kaye
(JA)
Ronald Kim
(R)
Neil W Kowall
(NW)
Joel H Kramer
(JH)
Brian W Kunkle
(BW)
Amanda P Kuzma
(AP)
Frank M LaFerla
(FM)
James J Lah
(JJ)
Yuk Ye Leung
(YY)
James B Leverenz
(JB)
Allan I Levey
(AI)
Ge Li
(G)
Andrew P Lieberman
(AP)
Richard B Lipton
(RB)
Oscar L Lopez
(OL)
Constantine G Lyketsos
(CG)
John Malamon
(J)
Daniel C Marson
(DC)
Eden R Martin
(ER)
Frank Martiniuk
(F)
Deborah C Mash
(DC)
Eliezer Masliah
(E)
Wayne C McCormick
(WC)
Susan M McCurry
(SM)
Andrew N McDavid
(AN)
Stefan McDonough
(S)
Ann C McKee
(AC)
Marsel Mesulam
(M)
Bruce L Miller
(BL)
Carol A Miller
(CA)
Joshua W Miller
(JW)
John C Morris
(JC)
Shubhabrata Mukherjee
(S)
Adam C Naj
(AC)
Sid O'Bryant
(S)
John M Olichney
(JM)
Joseph E Parisi
(JE)
Henry L Paulson
(HL)
Elaine Peskind
(E)
Ronald C Petersen
(RC)
Aimee Pierce
(A)
Wayne W Poon
(WW)
Huntington Potter
(H)
Liming Qu
(L)
Joseph F Quinn
(JF)
Ashok Raj
(A)
Murray Raskind
(M)
Barry Reisberg
(B)
Joan S Reisch
(JS)
Christiane Reitz
(C)
John M Ringman
(JM)
Erik D Roberson
(ED)
Ekaterina Rogaeva
(E)
Howard J Rosen
(HJ)
Roger N Rosenberg
(RN)
Donald R Royall
(DR)
Mark A Sager
(MA)
Mary Sano
(M)
Andrew J Saykin
(AJ)
Lon S Schneider
(LS)
William W Seeley
(WW)
Amanda G Smith
(AG)
Joshua A Sonnen
(JA)
Salvatore Spina
(S)
Peter St George-Hyslop
(PS)
Robert A Stern
(RA)
Russell H Swerdlow
(RH)
Rudolph E Tanzi
(RE)
Juan C Troncoso
(JC)
Debby W Tsuang
(DW)
Otto Valladares
(O)
Vivianna M Van Deerlin
(VM)
Linda J Van Eldik
(LJ)
Badri N Vardarajan
(BN)
Harry V Vinters
(HV)
Sandra Weintraub
(S)
Kathleen A Welsh-Bohmer
(KA)
Kirk C Wilhelmsen
(KC)
Jennifer Williamson
(J)
Thomas S Wingo
(TS)
Randall L Woltjer
(RL)
Clinton B Wright
(CB)
Chuang-Kuo Wu
(CK)
Chang-En Yu
(CE)
Lei Yu
(L)
Yi Zhao
(Y)
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