Polygenic hazard scores in preclinical Alzheimer disease.

TitlePolygenic hazard scores in preclinical Alzheimer disease.
Publication TypeJournal Article
Year of Publication2017
AuthorsTan CHong, Hyman BT, Tan JJX, Hess CP, Dillon WP, Schellenberg GD, Besser LM, Kukull WA, Kauppi K, McEvoy LK, Andreassen OA, Dale AM, Fan CChieh, Desikan RS
JournalAnn Neurol
Volume82
Issue3
Pagination484-488
Date Published2017 Sep
ISSN1531-8249
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Apolipoprotein E4, Disease Progression, Female, Genetic Predisposition to Disease, Genotype, Humans, Longitudinal Studies, Male, Multifactorial Inheritance, Neuropsychological Tests, Risk Assessment, Risk Factors
Abstract

Identifying asymptomatic older individuals at elevated risk for developing Alzheimer disease (AD) is of clinical importance. Among 1,081 asymptomatic older adults, a recently validated polygenic hazard score (PHS) significantly predicted time to AD dementia and steeper longitudinal cognitive decline, even after controlling for APOE ɛ4 carrier status. Older individuals in the highest PHS percentiles showed the highest AD incidence rates. PHS predicted longitudinal clinical decline among older individuals with moderate to high Consortium to Establish a Registry for Alzheimer's Disease (amyloid) and Braak (tau) scores at autopsy, even among APOE ɛ4 noncarriers. Beyond APOE, PHS may help identify asymptomatic individuals at highest risk for developing Alzheimer neurodegeneration. Ann Neurol 2017;82:484-488.
DOI10.1002/ana.25029
Alternate JournalAnn. Neurol.
PubMed ID28940650
PubMed Central IDPMC5758043
Grant ListP50 AG005134 / AG / NIA NIH HHS / United States
U01 AG016976 / AG / NIA NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States