Evidence map›Paper›PMID 40704449›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Exploring potential mechanisms of an African protective locus for Alzheimer's disease in APOEε4 carriers.

Luciana Bertholim-Nasciben, Karen Nuytemans, Derek Van Booven, Farid Rajabli, Sofia Moura, Aura M Ramirez, Griffin S Parker, Derek M Dykxhoorn, Liyong Wang, William K Scott and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Ancestry-specific effects ofmedRxiv : the preprint server for health sciences · 2026
    Article
  2. Exploring potential mechanisms of an African protective locus for Alzheimer's disease in APOEε4 carriers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Luciana Bertholim-NascibenHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.ORCID 0009-0002-1518-1409
Karen NuytemansHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Derek Van BoovenHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Farid RajabliHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Sofia MouraHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Aura M RamirezHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Griffin S ParkerHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Derek M DykxhoornHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Liyong WangHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
William K ScottHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
David A DavisBrain Endowment Bank, Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida, USA.
Regina T VontellBrain Endowment Bank, Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida, USA.
Katalina F McInerneyDepartment of Neurology, Miller School of Medicine, Miami, Florida, USA.
Michael L CuccaroHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Goldie S ByrdMaya Angelou Center for Health Equity, Wake Forest University, Winston-Salem, North Carolina, USA.
Jonathan L HainesCleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA.
Marla GearingGoizueta Alzheimer's Disease Research Center, Emory University, Atlanta, Georgia, USA.
Larry D AdamsHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Margaret A Pericak-VanceHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Juan I YoungHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Anthony J GriswoldHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.
Jeffery M VanceHussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA.

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Large Scale Genome SequencingU54HG003079 · NHGRI · WASHINGTON UNIVERSITY · PI DUTCHER, SUSAN K · 2004 to 2016
$445.7M
The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3M
Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI MONICA G. RIVERA-MINDT · 2016 to 2026
$226.7M
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
VCID and Stroke in a Bi-racial National CohortU01NS041588 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CUSHMAN, MARY, HOWARD, GEORGE · 2002 to 2022
$96.0M
Translational pharmacoepidemiology: neuroprotection and neurotoxicity of antihypertensives and strong anticholinergicsU19AG066567 · NIA · KAISER FOUNDATION RESEARCH INSTITUTE · PI Christine L MacDonald · 2021 to 2026
$80.4M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
ARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2M
Alzheimer's Association Research Fellowship to Promote Diversity AARFD-24-1309441BrightFocus foundation A2018425SNHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54 HG003079NHGRI NIH HHS U54 HG003273NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS R01 HL070825NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL172803NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL096812NHLBI NIH HHS U01 HL096814NHLBI NIH HHS U01 HL096899NHLBI NIH HHS U01 HL096902NHLBI NIH HHS U01 HL096917NHLBI NIH HHS U01 HL130114NIA NIH HHS K23 AG030944NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS P20 AG068024NIA NIH HHS P20 AG068053NIA NIH HHS P20 AG068077NIA NIH HHS P20 AG068082NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG038072NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG062715NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066468NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066508NIA NIH HHS P30 AG066509NIA NIH HHS P30 AG066511NIA NIH HHS P30AG066511NIA NIH HHS P30 AG066512NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066519NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG066546NIA NIH HHS P30 AG072931NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072958NIA NIH HHS P30 AG072959NIA NIH HHS P30 AG072972NIA NIH HHS P30 AG072973NIA NIH HHS P30 AG072975NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072978NIA NIH HHS P30 AG072979NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG008012NIA NIH HHS P50 AG016574NIA NIH HHS R01 AG009029NIA NIH HHS R01 AG009956NIA NIH HHS R01 AG011101NIA NIH HHS R01 AG011380NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG015928NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG018016NIA NIH HHS R01 AG019085NIA NIH HHS R01 AG019757NIA NIH HHS R01 AG019771NIA NIH HHS R01 AG020098NIA NIH HHS R01 AG021136NIA NIH HHS R01 AG021547NIA NIH HHS R01 AG022018NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG025259NIA NIH HHS R01 AG027161NIA NIH HHS R01 AG027944NIA NIH HHS R01 AG028786NIA NIH HHS R01 AG031272NIA NIH HHS R01 AG032289NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG033040NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG041797NIA NIH HHS R01 AG042188NIA NIH HHS R01 AG042210NIA NIH HHS R01 AG044546NIA NIH HHS R01 AG044829NIA NIH HHS R01 AG046949NIA NIH HHS R01 AG048234NIA NIH HHS R01 AG048927NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054047NIA NIH HHS R01 AG054076NIA NIH HHS R01 AG057909NIA NIH HHS R01 AG059716NIA NIH HHS R01 AG060747NIA NIH HHS R01 AG061155NIA NIH HHS R01 AG064614NIA NIH HHS R01 AG064877NIA NIH HHS R01 AG070864NIA NIH HHS R01AG070864NIA NIH HHS R01 AG072547NIA NIH HHS R01AG072547NIA NIH HHS R01 AG079280NIA NIH HHS R01AG15819NIA NIH HHS R37 AG015473NIA NIH HHS R56 AG051876NIA NIH HHS RC4 AG039085NIA NIH HHS RF1 AG015473NIA NIH HHS RF1 AG051504NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG054023NIA NIH HHS RF1 AG054047NIA NIH HHS RF1 AG054052NIA NIH HHS RF1 AG054074NIA NIH HHS RF1 AG054080NIA NIH HHS RF1 AG057519NIA NIH HHS RF1 AG058066NIA NIH HHS RF1 AG058267NIA NIH HHS RF1 AG058501NIA NIH HHS RF1 AG059018NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG049506NIA NIH HHS U01 AG049507NIA NIH HHS U01 AG049508NIA NIH HHS U01 AG052409NIA NIH HHS U01 AG052410NIA NIH HHS U01AG052410NIA NIH HHS U01 AG052411NIA NIH HHS U01 AG057659NIA NIH HHS U01 AG058589NIA NIH HHS U01 AG058635NIA NIH HHS U01 AG058654NIA NIH HHS U01 AG058922NIA NIH HHS U01 AG062602NIA NIH HHS U01 AG062943NIA NIH HHS U01 AG066767NIA NIH HHS U01AG066767NIA NIH HHS U01 AG068057NIA NIH HHS U01 AG072579NIA NIH HHS U01AG072579NIA NIH HHS U01 AG084545NIA NIH HHS U19 AG024904NIA NIH HHS U19 AG066567NIA NIH HHS U19 AG074865NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG041689NIA NIH HHS U24 AG056270NIA NIH HHS U24 AG072122NIA NIH HHS U24 AG074855NIA NIH HHS U54 AG052427NIA NIH HHS UF1 AG047133NINDS NIH HHS P01 NS026630NINDS NIH HHS P50 NS039764NINDS NIH HHS P50 NS071674NINDS NIH HHS R01 NS017950NINDS NIH HHS R01 NS029993NINDS NIH HHS R01 NS069719NINDS NIH HHS R01 NS080820NINDS NIH HHS U01 NS041588Wellcome TrustZenith Award
6 · The paper itself

Abstract

introductionWe recently described that the African-specific A allele of rs10423769, which lies in an area of segmental duplications, reduces Alzheimer's disease (AD) risk by ∼ 75% in apolipoprotein E (APOE) ε4 homozygotes.

methodsShort and long-read sequencing were used to identify the haplotype harboring rs10423769_A and examine DNA methylation and structural variation (SV).

resultsA unique 21 kb haplotype is shared amongst all rs10423769_A carriers (r DISCUSSION: The protective haplotype is unique, with haplotype changes in DNA methylation and SV that could contribute to the protective mechanism of rs10423769_A. The study generates hypothesis for future studies on this important protective mechanism for APOEε4 carriers. HIGHLIGHTS: We investigated an African-specific haplotype harboring a protective locus for APOEε4 carriers that significantly reduces the risk for Alzheimer Disease. The protective locus lies in an area of segmental duplications 2MB from APOE. We found that the protective haplotype is unique within the segmental duplications. The haplotype is found in all African ancestry tested but not in other ancestries. Long read whole genome sequencing identified an expanded VNTR associated with the protective haplotype containing multiple MEF2 transcription factor binding motifs. Differences in DNA methylation were found between the protective and the reference haplotype.

Indexed as

Alzheimer DiseaseApolipoprotein E4Black PeopleGenetic Predisposition to DiseaseAgedAllelesDNA MethylationFemaleHaplotypesHeterozygoteHumansMaleMinisatellite RepeatsPolymorphism, Single NucleotideApolipoprotein E4Alzheimer's diseasegenetic ancestryhaplotypelong‐read sequencingmethylationprotective variantstructural variation

Identifiers

PMID40704449
PMCPMC12287753

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.