Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds.
APOE
Alzheimer's disease
local ancestry
single-nucleus RNA-seq
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
02
12
2020
received:
02
06
2020
accepted:
06
12
2020
pubmed:
2
2
2021
medline:
19
11
2021
entrez:
1
2
2021
Statut:
ppublish
Résumé
Apolipoprotein E (APOE) ε4 confers less risk for Alzheimer's disease (AD) in carriers with African local genomic ancestry (ALA) than APOE ε4 carriers with European local ancestry (ELA). Cell type specific transcriptional variation between the two local ancestries (LAs) could contribute to this disease risk differences. Single-nucleus RNA sequencing was performed on frozen frontal cortex of homozygous APOE ε4/ε4 AD patients: seven with ELA, four with ALA. A total of 60,908 nuclei were sequenced. Within the LA region (chr19:44-46Mb), APOE was the gene most differentially expressed, with ELA carriers having significantly more expression (overall P < 1.8E AD patients with ELA expressed significantly greater levels of APOE than ALA APOE ε4 carriers. These differences in APOE expression could contribute to the reduced risk for AD seen in African APOE ε4 carriers.
Identifiants
pubmed: 33522086
doi: 10.1002/alz.12287
pmc: PMC8843031
mid: NIHMS1657410
doi:
Substances chimiques
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
1179-1188Subventions
Organisme : NIA NIH HHS
ID : U01 AG058654
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066511
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG054074
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG057659
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : NIH HHS
ID : P30-AG013854
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG025688
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG052410
Pays : United States
Organisme : NIH HHS
ID : P50-AG0256878
Pays : United States
Organisme : NIA NIH HHS
ID : U01-AG057659
Pays : United States
Organisme : NIA NIH HHS
ID : RF1-AG054074
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013854
Pays : United States
Organisme : NIA NIH HHS
ID : U01-AG052410
Pays : United States
Organisme : NIA NIH HHS
ID : R01-AG059018
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG059018
Pays : United States
Informations de copyright
© 2021 the Alzheimer's Association.
Références
Am J Hum Genet. 2013 Aug 8;93(2):278-88
pubmed: 23910464
Alzheimers Dement. 2019 Dec;15(12):1524-1532
pubmed: 31606368
Nature. 2017 Jan 26;541(7638):481-487
pubmed: 28099414
Neuron. 2013 Dec 18;80(6):1347-58
pubmed: 24360540
Nature. 2017 Sep 28;549(7673):523-527
pubmed: 28959956
Neurol Genet. 2020 Mar 3;6(2):e404
pubmed: 32337333
Bioinformatics. 2005 Jan 15;21(2):263-5
pubmed: 15297300
JAMA Neurol. 2021 Jan 1;78(1):102-113
pubmed: 33074286
Neurosci Lett. 1997 Jul 4;229(3):157-60
pubmed: 9237482
JAMA. 1997 Oct 22-29;278(16):1349-56
pubmed: 9343467
BMC Bioinformatics. 2013 Apr 15;14:128
pubmed: 23586463
JAMA. 1998 Mar 11;279(10):751-5
pubmed: 9508150
BMC Med Genomics. 2019 Sep 9;12(1):128
pubmed: 31500627
Science. 1993 Aug 13;261(5123):921-3
pubmed: 8346443
Sci Rep. 2017 Oct 25;7(1):13988
pubmed: 29070875
Neurosci Lett. 2018 Apr 13;672:53-58
pubmed: 29474873
J Neurosci. 2012 May 2;32(18):6391-410
pubmed: 22553043
BMC Med Genomics. 2018 May 8;11(1):43
pubmed: 29739406
Int Psychogeriatr. 2014 Jun;26(6):977-85
pubmed: 24565289
Arch Neurol. 2002 Apr;59(4):594-600
pubmed: 11939894
Immunity. 2017 Jun 20;46(6):957-967
pubmed: 28636962
Neuron. 2019 Mar 6;101(5):820-838
pubmed: 30844401
Nat Methods. 2018 Apr;15(4):255-261
pubmed: 29481549
Nat Genet. 2011 May;43(5):491-8
pubmed: 21478889
Nat Biotechnol. 2018 Jun;36(5):411-420
pubmed: 29608179
Biochem Biophys Res Commun. 2004 Aug 6;320(4):1051-4
pubmed: 15249195
Nat Commun. 2014 Jun 13;5:3934
pubmed: 25653097
Hum Mol Genet. 2004 Nov 15;13(22):2885-92
pubmed: 15385439
JAMA. 2013 Apr 10;309(14):1483-92
pubmed: 23571587
Ann Neurol. 1997 Oct;42(4):659-61
pubmed: 9382479
Proc Natl Acad Sci U S A. 2018 Feb 20;115(8):E1896-E1905
pubmed: 29437957
Nature. 2015 Oct 1;526(7571):68-74
pubmed: 26432245
Am J Hum Genet. 1996 Mar;58(3):574-84
pubmed: 8644717
J Alzheimers Dis. 2015;46(3):553-69
pubmed: 25812852
Nat Genet. 2019 Mar;51(3):414-430
pubmed: 30820047
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
PLoS Genet. 2018 Dec 5;14(12):e1007791
pubmed: 30517106
Nat Commun. 2019 Apr 3;10(1):1523
pubmed: 30944313
Neuron. 2017 Dec 6;96(5):1013-1023.e4
pubmed: 29216448
Neurology. 2001 Jan 9;56(1):49-56
pubmed: 11148235
Genome Biol. 2015 Dec 10;16:278
pubmed: 26653891
Hum Mol Genet. 2020 May 8;29(7):1154-1167
pubmed: 32160291