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Pathway-Specific Genetic Risk for Alzheimer’s Disease Differentiates Regional Patterns of Cortical Atrophy in Older Adults
Journal article

Pathway-Specific Genetic Risk for Alzheimer’s Disease Differentiates Regional Patterns of Cortical Atrophy in Older Adults

  • Caspers, Svenja JARA-BRAIN, Jülich-Aachen Research Alliance, Jülich, Germany
  • Röckner, Melanie E Institute of Human Genetics, University Hospital Bonn, Bonn, Germany
  • Jockwitz, Christiane Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Medical Faculty, Aachen, Germany
  • Bittner, Nora Institute for Anatomy I, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
  • Teumer, Alexander Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
  • Herms, Stefan Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
  • Hoffmann, Per Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
  • Nöthen, Markus M Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
  • Moebus, Susanne Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen, Germany
  • Amunts, Katrin C. & O. Vogt Institute for Brain Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
  • Cichon, Sven Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
  • Mühleisen, Thomas W C. & O. Vogt Institute for Brain Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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  • 2019-8-9
Published in:
  • Cerebral Cortex. - Oxford University Press (OUP). - 2019
Cognitive Neuroscience
Cellular and Molecular Neuroscience
English Abstract
Brain aging is highly variable and represents a challenge to delimit aging from disease processes. Moreover, genetic factors may influence both aging and disease. Here we focused on this issue and investigated effects of multiple genetic loci previously identified to be associated with late-onset Alzheimer’s disease (AD) on brain structure of older adults from a population sample. We calculated a genetic risk score (GRS) using genome-wide significant single-nucleotide polymorphisms from genome-wide association studies of AD and tested its effect on cortical thickness (CT). We observed a common pattern of cortical thinning (right inferior frontal, left posterior temporal, medial occipital cortex). To identify CT changes by specific biological processes, we subdivided the GRS effect according to AD-associated pathways and performed follow-up analyses. The common pattern from the main analysis was further differentiated by pathway-specific effects yielding a more bilateral pattern. Further findings were located in the superior parietal and mid/anterior cingulate regions representing 2 unique pathway-specific patterns. All patterns, except the superior parietal pattern, were influenced by apolipoprotein E. Our step-wise approach revealed atrophy patterns that partially resembled imaging findings in early stages of AD. Our study provides evidence that genetic burden for AD contributes to structural brain variability in normal aging.
Language
  • English
Open access status
hybrid
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Persistent URL
https://sonar.ch/global/documents/5855
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