| Autor: |
Scholz CJ; Core Unit Systems Medicine, University Hospital of Würzburg, Würzburg, Germany., Weber H; Department of Psychiatry, Psychosomatics, Psychotherapy, University Hospital Frankfurt/Main, Frankfurt/Main, Germany.; Center of Mental Health, Clinic and Policlinic of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany., Jungwirth S; Ludwig Boltzmann Society, L. Boltzmann Institute of Aging Research, Vienna, Austria.; Department of Psychiatry, Social Medicine Center East- Donauspital, Vienna, Austria., Danielczyk W; Ludwig Boltzmann Society, L. Boltzmann Institute of Aging Research, Vienna, Austria., Reif A; Department of Psychiatry, Psychosomatics, Psychotherapy, University Hospital Frankfurt/Main, Frankfurt/Main, Germany., Tragl KH; Ludwig Boltzmann Society, L. Boltzmann Institute of Aging Research, Vienna, Austria., Fischer P; Ludwig Boltzmann Society, L. Boltzmann Institute of Aging Research, Vienna, Austria.; Department of Psychiatry, Social Medicine Center East- Donauspital, Vienna, Austria., Riederer P; Center of Mental Health, Clinic and Policlinic of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany., Deckert J; Center of Mental Health, Clinic and Policlinic of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany., Grünblatt E; Center of Mental Health, Clinic and Policlinic of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany. edna.gruenblatt@kjpd.uzh.ch.; Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Wagistrasse 12, Schlieren, 8952, Zurich, Switzerland. edna.gruenblatt@kjpd.uzh.ch. |
| Abstrakt: |
Alzheimer's disease (AD) is a neurodegenerative disorder that preferentially affects individuals of advanced age. Heritability estimates for AD range between 60 and 80%, but only few genetic risk factors have been identified so far. In the present explorative study, we aimed at characterizing the genetic contribution to late-onset AD in participants of the Vienna Transdanube Aging (VITA) longitudinal birth cohort study in a two-step approach. First, we performed a genome-wide screen of pooled DNA samples (n = 588) to identify allele frequency differences between AD patients and non-AD individuals using life-time diagnoses made at the age of 80 (t = 60 months). This analysis suggested a high proportion of brain-expressed genes required for cell adhesion, cell signaling and cell morphogenesis, and also scored in known AD risk genes. In a second step, we confirmed associations using individual genotypes of top-ranked markers examining AD diagnoses as well as the dimensional scores: FULD and MMSE determined up to the age of 82.5 (t = 90 months). Taken together, our study proposes genes ANKS1B, ENST00000414107, LOC100505811, SLC22A14, QRFPR, ZDHHC8P1, ADAMTS3 and PPFIA1 as possible new candidates involved in the etiology of late-onset AD, with further research being needed to clarify their exact roles. |
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