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

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• 作者：Eva Louwersheimerp>ap>p> ; p>p>1p>p> ; p>p>e.louwersheimer@vumc.nl" class="auth_mail" title="E-mail the corresponding authorp> ; Steffen Wolfsgruberp>bp>p> ; p>p>cp>p> ; p>p>1p> ; Ana Espinosap>dp> ; André ; Lacourp>cp> ; Stefanie Heilmann-Heimbachp>ep>p> ; p>p>fp> ; Montserrat Alegretp>dp> ; Isabel Herná ; ndezp>dp> ; Maité ; e Rosende-Rocap>dp> ; Lluí ; s Tá ; rragap>dp> ; Mercè ; Boadap>dp> ; Johannes Kornhuberp>gp> ; Oliver Petersp>hp> ; Lutz Frö ; lichp>ip> ; Michael Hü ; llp>jp> ; Eckart Rü ; therp>kp> ; Jens Wiltfangp>kp> ; Martin Schererp>lp> ; Steffi Riedel-Hellerp>mp> ; Frank Jessenp>np> ; Markus M. Nö ; thenp>ep>p> ; p>p>fp> ; Wolfgang Maierp>bp>p> ; p>p>cp> ; Ted Koenep>ap>p> ; p>p>op> ; Philip Scheltensp>ap> ; Henne Holstegep>pp> ; Michael Wagnerp>bp>p> ; p>p>cp> ; Agustí ; n Ruizp>dp> ; Wiesje M. van der Flierp>ap>p> ; p>p>qp> ; Tim Beckerp>rp> ; Alfredo Ramirezp>bp>p> ; p>p>ep>p> ; p>p>alfredo.ramirez@ukb.uni-bonn.de" class="auth_mail" title="E-mail the corresponding authorp>
• 关键词：Alzheimer's disease ; Mild cognitive impairment ; Polygenic risk score ; Endophenotypes ; Genetic risk variants
• 刊名：Alzheimer's & Dementia
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：12
• 期：8
• 页码：872-881
• 全文大小：619 K

文摘

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).p>

Methods

<p id="abspara0015">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 (aβ, tau, ptau).p>

Results

<p id="abspara0020">PGS was modestly associated with cognitive decline over time, as measured by mini-mental state examination (MMSE) (β &plusmn; SE:−0.24 &plusmn; 0.10; P = .012), and with CSF levels of tau and ptau (tau: 1.38 &plusmn; 0.36, P = 1.21 × 10p>−4p>; ptau: 1.40 &plusmn; 0.36, P = 1.02 × 10p>−4p>).p>

Discussion

<p id="abspara0025">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.