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

Polygenic hazard scores in preclinical Alzheimer disease

Chin Hong Tan  1 , Bradley T Hyman  2 , Jacinth J X Tan  3 , Christopher P Hess  1 , William P Dillon  1 , Gerard D Schellenberg  4 , Lilah M Besser  5 , Walter A Kukull  5 , Karolina Kauppi  6 , Linda K McEvoy  6 , Ole A Andreassen  7 , Anders M Dale  6   8   9 , Chun Chieh Fan  9 , Rahul S Desikan  1   10
Affiliations

Polygenic hazard scores in preclinical Alzheimer disease

Chin Hong Tan et al. Ann Neurol. 2017 Sep.

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.

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Conflict of interest statement

POTENTIAL RELEVANT CONFLICTS OF INTEREST

None

Figures

Figure 1
Figure 1
Annualized or cumulative incidence rates in CN individuals showing the instantaneous hazard as a function of PHS percentiles and age.
Figure 2
Figure 2
Differences in change over time in CDR-SB in CN individuals over time for low (−1 SD, ~16 percentile) and high (+1 SD, ~84 percentile) polygenic hazard score (PHS) individuals. Dotted lines around fitted line indicate estimated standard error.
See this image and copyright information in PMC

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References

    1. Dubois B, Hampel H, Feldman HH, et al. Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria. Alzheimers Dement. 2016;12(3):292–323. - PMC - PubMed
    1. Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280–92. - PMC - PubMed
    1. Bu G. Apolipoprotein E and its receptors in Alzheimer’s disease: pathways, pathogenesis and therapy. Nat Rev Neurosci. 2009;10(5):333–344. https://doi.org/10.1038/nrn2620. - DOI - PMC - PubMed
    1. Bonham LW, Geier EG, Fan CC, et al. Age-dependent effects of APOE ε4 in preclinical Alzheimer’s disease. Ann Clin Transl Neurol. 2016;3(9):668–677. https://doi.org/10.1002/acn3.333. - DOI - PMC - PubMed
    1. Caselli RJ, Reiman EM, Locke DEC, et al. Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment. Arch Neurol. 2007;64(9):1306–1311. https://doi.org/10.1001/archneur.64.9.1306. - DOI - PubMed

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