Alzheimer's & dementia : the journal of the Alzheimer's Association · 2016
Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment.
СтатьяМетаанализПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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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
Аннотация
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.
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.
Предметные рубрики MeSH
AgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesApolipoproteins ECognitive DysfunctionCohort StudiesDatasets as TopicEndophenotypesFemaleHumansMaleMental Status ScheduleMiddle AgedMultifactorial InheritanceNeuropsychological TestsOdds RatioPolymorphism, Single NucleotideStatistics, Nonparametric