RT Journal Article
SR Electronic
T1 Polygenic hazard scores in preclinical Alzheimer’s disease
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 156331
DO 10.1101/156331
A1 Chin Hong Tan
A1 Leo P. Sugrue
A1 Iris J. Broce
A1 Elizabeth Tong
A1 Jacinth J. X. Tan
A1 Christopher P. Hess
A1 William P. Dillon
A1 Luke W. Bonham
A1 Jennifer S. Yokoyama
A1 Gil D. Rabinovici
A1 Howard J. Rosen
A1 Bruce L. Miller
A1 Bradley T. Hyman
A1 Gerard D. Schellenberg
A1 Lilah M. Besser
A1 Walter A. Kukull
A1 Celeste M. Karch
A1 James B. Brewer
A1 Karolina Kauppi
A1 Linda K. McEvoy
A1 Ole A. Andreassen
A1 Anders M. Dale
A1 Chun Chieh Fan
A1 Rahul S. Desikan
YR 2017
UL http://biorxiv.org/content/early/2017/06/27/156331.abstract
AB Identifying asymptomatic older individuals at elevated risk for developing Alzheimer’s 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 ε4 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 CERAD (amyloid) and Braak (tau) scores at autopsy, even among APOE ε4 non-carriers. Beyond APOE, PHS may help identify asymptomatic individuals at highest risk for developing Alzheimer’s neurodegeneration.