TY - JOUR T1 - Polygenic hazard scores in preclinical Alzheimer’s disease JF - bioRxiv DO - 10.1101/156331 SP - 156331 AU - Chin Hong Tan AU - Leo P. Sugrue AU - Iris J. Broce AU - Elizabeth Tong AU - Jacinth J. X. Tan AU - Christopher P. Hess AU - William P. Dillon AU - Luke W. Bonham AU - Jennifer S. Yokoyama AU - Gil D. Rabinovici AU - Howard J. Rosen AU - Bruce L. Miller AU - Bradley T. Hyman AU - Gerard D. Schellenberg AU - Lilah M. Besser AU - Walter A. Kukull AU - Celeste M. Karch AU - James B. Brewer AU - Karolina Kauppi AU - Linda K. McEvoy AU - Ole A. Andreassen AU - Anders M. Dale AU - Chun Chieh Fan AU - Rahul S. Desikan Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/06/27/156331.abstract N2 - 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. ER -