The executive prominent/memory prominent spectrum in Alzheimer's disease is highly heritable.

TitleThe executive prominent/memory prominent spectrum in Alzheimer's disease is highly heritable.
Publication TypeJournal Article
Year of Publication2016
AuthorsMez, J, Mukherjee, S, Thornton, T, Fardo, DW, Trittschuh, E, Sutti, S, Sherva, R, Kauwe, JS, Naj, AC, Beecham, GW, Gross, A, Saykin, AJ, Green, RC, Crane, PK
Corporate AuthorsExecutive Prominent Alzheimer's Disease: Genetics and Risk Factors (EPAD:GRF), Alzheimer's Disease Neuroimaging Initiative (ADNI1), Alzheimer's Disease Genetics Consortium (ADGC)
JournalNeurobiol Aging
Volume41
Pagination115-121
Date Published2016 May
ISSN1558-1497
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Chromosomes, Databases, Genetic, Executive Function, Female, Genetic Predisposition to Disease, Humans, Male, Memory, Phenotype, Polymorphism, Single Nucleotide
Abstract

Late-onset Alzheimer's disease (LOAD) can present heterogeneously, with several subtypes recognized, including dysexecutive AD. One way to identify people with dysexecutive AD is to consider the difference between memory and executive functioning, which we refer to as the executive prominent/memory prominent spectrum. We aimed to determine if this spectrum was heritable. We used neuropsychological and genetic data from people with mild LOAD (Clinical Dementia Rating 0.5 or 1.0) from the National Alzheimer's Coordinating Center and the Alzheimer's Disease Neuroimaging Initiative. We cocalibrated the neuropsychological data to obtain executive functioning and memory scores and used their difference as a continuous phenotype to calculate its heritability overall and by chromosome. Narrow-sense heritability of the difference between memory and executive functioning scores was 0.68 (standard error 0.12). Single nucleotide polymorphisms on chromosomes 1, 2, 4, 11, 12, and 18 explained the largest fraction of phenotypic variance, with signals from each chromosome accounting for 5%-7%. The chromosomal pattern of heritability differed substantially from that of LOAD itself.

DOI10.1016/j.neurobiolaging.2016.02.015
Alternate JournalNeurobiol. Aging
PubMed ID27103524
PubMed Central IDPMC4843522
Grant ListP50 MH060451 / MH / NIMH NIH HHS / United States
MH60451 / MH / NIMH NIH HHS / United States
UL1 TR001445 / TR / NCATS NIH HHS / United States
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