Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment
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
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Alzheimer's and dementia. - 12, 8 (2016) , 872-881, ISSN: 1552-5279
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2021
- DOI
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10.1016/j.jalz.2016.01.006
- URN
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urn:nbn:de:bsz:25-freidok-1750480
- Rechteinformation
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Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
-
25.03.2025, 13:53 MEZ
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Beteiligte
- Louwersheimer, Eva
- Hüll, Michael
- Ramírez, Alfredo
- Universität
Entstanden
- 2021
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