Short-term memory advantage for brief durations in human APOE ε4 carriers.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
11 06 2020
Historique:
received: 01 12 2019
accepted: 07 05 2020
entrez: 13 6 2020
pubmed: 13 6 2020
medline: 15 12 2020
Statut: epublish

Résumé

The Apolipoprotein-E (APOE) ε4 gene allele, the highest known genetic risk factor for Alzheimer's disease, has paradoxically been well preserved in the human population. One possible explanation offered by evolutionary biology for survival of deleterious genes is antagonistic pleiotropy. This theory proposes that such genetic variants might confer an advantage, even earlier in life when humans are also reproductively fit. The results of some small-cohort studies have raised the possibility of such a pleiotropic effect for the ε4 allele in short-term memory (STM) but the findings have been inconsistent. Here, we tested STM performance in a large cohort of individuals (N = 1277); nine hundred and fifty-nine of which included carrier and non-carriers of the APOE ε4 gene, those at highest risk of developing Alzheimer's disease. We first confirm that this task is sensitive to subtle deterioration in memory performance across ageing. Importantly, individuals carrying the APOE ε4 gene actually exhibited a significant memory advantage across all ages, specifically for brief retention periods but crucially not for longer durations. Together, these findings present the strongest evidence to date for a gene having an antagonistic pleiotropy effect on human cognitive function across a wide age range, and hence provide an explanation for the survival of the APOE ε4 allele in the gene pool.

Identifiants

pubmed: 32528115
doi: 10.1038/s41598-020-66114-6
pii: 10.1038/s41598-020-66114-6
pmc: PMC7289888
doi:

Substances chimiques

Apolipoproteins E 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

9503

Subventions

Organisme : Wellcome Trust
ID : 203130/Z/16/Z
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 098282/Z/12/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P00878X/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 104571/Z/14/Z
Pays : United Kingdom

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Auteurs

Nahid Zokaei (N)

Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, UK. nahid.zokaei@psy.ox.ac.uk.
Department of Experimental Psychology, University of Oxford, Oxford, OX1 3UD, UK. nahid.zokaei@psy.ox.ac.uk.

John Grogan (J)

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.

Sean James Fallon (SJ)

National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol NHS foundation Trust and University of Bristol, Oxford, UK.

Ellie Slavkova (E)

Department of Experimental Psychology, University of Oxford, Oxford, OX1 3UD, UK.

Jonathan Hadida (J)

Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, UK.

Sanjay Manohar (S)

Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.

Anna Christina Nobre (AC)

Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry, University of Oxford, Oxford, OX3 7JX, UK.
Department of Experimental Psychology, University of Oxford, Oxford, OX1 3UD, UK.

Masud Husain (M)

Department of Experimental Psychology, University of Oxford, Oxford, OX1 3UD, UK.
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
Oxford NIHR Biomedical Research Centre, Oxford, UK.

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