Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment. Issue 8 (24th February 2016)

• Record Type: Journal Article
• Authors: Louwersheimer, Eva; Wolfsgruber, Steffen; Espinosa, Ana; Lacour, André; Heilmann‐Heimbach, Stefanie; Alegret, Montserrat; Hernández, Isabel; Rosende‐Roca, Maitée; Tárraga, Lluís; Boada, Mercè; Kornhuber, Johannes; Peters, Oliver; Frölich, Lutz; Hüll, Michael; Rüther, Eckart; Wiltfang, Jens; Scherer, Martin; Riedel‐Heller, Steffi; Jessen, Frank; Nöthen, Markus M.; Maier, Wolfgang; Koene, Ted; Scheltens, Philip; Holstege, Henne; Wagner, Michael; Ruiz, Agustín; van der Flier, Wiesje M.; Becker, Tim; Ramirez, Alfredo
• Is Part Of: Alzheimer's & dementia. Volume 12:Issue 8(2016)
• Page Start: 872
• Page End: 881
• Publication Date: 2016-02-24
• Subjects: Alzheimer's disease -- Mild cognitive impairment -- Polygenic risk score -- Endophenotypes -- Genetic risk variants; Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1016/j.jalz.2016.01.006
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Introduction: 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). Methods: 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). Results: PGS was modestly associated with cognitive decline over time, as measured by mini‐mental state examination (MMSE) (β ± 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 ). Discussion: 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.