Polygenic hazard scores in preclinical Alzheimer disease

Chin Hong Tan; Bradley T Hyman; Jacinth J X Tan; Christopher P Hess; William P Dillon; Gerard D Schellenberg; Lilah M Besser; Walter A Kukull; Karolina Kauppi; Linda K McEvoy; Ole A Andreassen; Anders M Dale; Chun Chieh Fan; Rahul S Desikan

doi:10.1002/ana.25029

Polygenic hazard scores in preclinical Alzheimer disease

Ann Neurol. 2017 Sep;82(3):484-488. doi: 10.1002/ana.25029.

Authors

Chin Hong Tan¹, Bradley T Hyman², Jacinth J X Tan³, Christopher P Hess¹, William P Dillon¹, Gerard D Schellenberg⁴, Lilah M Besser⁵, Walter A Kukull⁵, Karolina Kauppi⁶, Linda K McEvoy⁶, Ole A Andreassen⁷, Anders M Dale^{6

8

9}, Chun Chieh Fan⁹, Rahul S Desikan^{1

10}

Affiliations

¹ Neuroradiology Section, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA.
² Department of Neurology, Massachusetts General Hospital, Boston, MA.
³ Center for Health and Community, University of California, San Francisco, San Francisco, CA.
⁴ Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
⁵ National Alzheimer's Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA.
⁶ Department of Radiology, University of California, San Diego, La Jolla, CA.
⁷ NORMENT Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁸ Department of Neurosciences, University of California, San Diego, La Jolla, CA.
⁹ Department of Cognitive Science, University of California, San Diego, La Jolla, CA.
¹⁰ Department of Neurology, University of California, San Francisco, San Francisco, CA.

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.

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / genetics*
Apolipoprotein E4 / genetics*
Disease Progression
Female
Genetic Predisposition to Disease*
Genotype
Humans
Longitudinal Studies
Male
Multifactorial Inheritance*
Neuropsychological Tests
Risk Assessment
Risk Factors

Substances

Apolipoprotein E4

Abstract

MeSH terms

Substances

Grants and funding