Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment

Louwersheimer E, Wolfsgruber S, Espinosa A, Lacour A, Heilmann-Heimbach S, Alegret M, Hernandez I, Rosende-Roca M, Tarraga L, Boada M, Kornhuber J, Peters O, Frolich L, Hull M, Ruther E, Wiltfang J, Scherer M, Riedel-Heller S, Jessen F, Nothen MM, Maier W, Koene T, Scheltens P, Holstege H, Wagner M, Ruiz A, Van Der Flier WM, Becker T, Ramirez A (2016)


Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 12

Pages Range: 872-81

Journal Issue: 8

DOI: 10.1016/j.jalz.2016.01.006

Abstract

We evaluated the effect of Alzheimer's disease (AD) susceptibility loci on endophenotypes closely related with AD pathology in patients with mild cognitive impairment (MCI).We selected 1730 MCI patients from four independent data sets. Weighted polygenic risk scores (PGS) were constructed of 18 non-apolipoprotein E (APOE) AD risk variants. In addition, we determined APOE genotype. AD endophenotypes were cognitive decline over time and cerebrospinal fluid (CSF) biomarkers (a?, tau, ptau).PGS was modestly associated with cognitive decline over time, as measured by mini-mental state examination (MMSE) (? ± SE:-0.24 ± 0.10; P = .012), and with CSF levels of tau and ptau (tau: 1.38 ± 0.36, P = 1.21 × 10(-4); ptau: 1.40 ± 0.36, P = 1.02 × 10(-4)).In MCI, we observed a joint effect of AD susceptibility loci on nonamyloid endophenotypes, suggesting a link of these genetic loci with neuronal degeneration in general rather than with Alzheimer-related amyloid deposition.

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APA:

Louwersheimer, E., Wolfsgruber, S., Espinosa, A., Lacour, A., Heilmann-Heimbach, S., Alegret, M.,... Ramirez, A. (2016). Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment. Alzheimers & Dementia, 12(8), 872-81. https://dx.doi.org/10.1016/j.jalz.2016.01.006

MLA:

Louwersheimer, Eva, et al. "Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment." Alzheimers & Dementia 12.8 (2016): 872-81.

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