Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment
| Autor: | André Lacour, Wiesje M. van der Flier, Eva Louwersheimer, Michael Hüll, Steffen Wolfsgruber, Frank Jessen, Tim Becker, Alfredo Ramirez, Eckart Rüther, Ana Espinosa, Henne Holstege, Maitée Rosende-Roca, Martin Scherer, Lluís Tárraga, Michael Wagner, Lutz Frölich, Ted Koene, Johannes Kornhuber, Markus M. Nöthen, Wolfgang Maier, Mercè Boada, Stefanie Heilmann-Heimbach, Jens Wiltfang, Montserrat Alegret, Philip Scheltens, Oliver Peters, Agustín Ruiz, Steffi G. Riedel-Heller, Isabel Hernández |
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| Přispěvatelé: | Neurology, Amsterdam Neuroscience - Neurodegeneration, Human genetics, Epidemiology and Data Science |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male Multifactorial Inheritance Epidemiology Datasets as Topic cerebrospinal fluid [Amyloid beta-Peptides] Disease Neuropsychological Tests Cohort Studies 0302 clinical medicine Cerebrospinal fluid Genotype Odds Ratio Cognitive decline Cognitive impairment genetics [Multifactorial Inheritance] Aged 80 and over Health Policy cerebrospinal fluid [Endophenotypes] diagnosis [Alzheimer Disease] Middle Aged cerebrospinal fluid [Alzheimer Disease] cerebrospinal fluid [Cognitive Dysfunction] Psychiatry and Mental health statistics & numerical data [Datasets as Topic] genetics [Polymorphism Single Nucleotide] Female complications [Cognitive Dysfunction] Psychology medicine.medical_specialty Endophenotypes Polymorphism Single Nucleotide Statistics Nonparametric 03 medical and health sciences Cellular and Molecular Neuroscience Apolipoproteins E Developmental Neuroscience Alzheimer Disease Internal medicine mental disorders medicine Humans Cognitive Dysfunction ddc:610 Aged Amyloid beta-Peptides genetics [Cognitive Dysfunction] 030104 developmental biology Endocrinology Endophenotype Disease risk genetics [Apolipoproteins E] Neurology (clinical) Geriatrics and Gerontology Mental Status Schedule Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Alzheimer's and dementia 12(8), 872-881 (2016). doi:10.1016/j.jalz.2016.01.006 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, M M, Maier, W, Koene, T, Scheltens, P, Holstege, H, Wagner, M, Ruiz, A, van der Flier, W M, Becker, T & Ramirez, A 2016, ' Alzheimer's disease risk variants modulate endophenotypes in mild cognitive impairment ', Alzheimers & Dementia, vol. 12, no. 8, pp. 872-881 . https://doi.org/10.1016/j.jalz.2016.01.006 Alzheimers & Dementia, 12(8), 872-881. Elsevier |
| ISSN: | 1552-5279 1552-5260 |
| DOI: | 10.1016/j.jalz.2016.01.006 |
| Popis: | IntroductionWe evaluated the effect of Alzheimer's disease (AD) susceptibility loci on endophenotypes closely related with AD pathology in patients with mild cognitive impairment (MCI).MethodsWe 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).ResultsPGS 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).DiscussionIn 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. |
| Databáze: | OpenAIRE |
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