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Differential patter...
Differential patterns of gray matter volumes and associated gene expression profiles in cognitively-defined Alzheimer's disease subgroups
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- Groot, Colin (author)
- Amsterdam UMC - Vrije Universiteit Amsterdam
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- Grothe, Michel J. (author)
- University Hospital Virgen del Rocío,German Center for Neurodegenerative Diseases (DZNE), Bonn
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- Mukherjee, Shubhabrata (author)
- University of Washington
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- Jelistratova, Irina (author)
- German Center for Neurodegenerative Diseases (DZNE), Bonn
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- Jansen, Iris (author)
- Vrije Universiteit Amsterdam
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- van Loenhoud, Anna Catharina (author)
- Amsterdam UMC - Vrije Universiteit Amsterdam
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- Risacher, Shannon L. (author)
- Indiana University
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- Saykin, Andrew J. (author)
- Indiana University
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- Mac Donald, Christine L. (author)
- University of Washington
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- Mez, Jesse (author)
- Boston University
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- Trittschuh, Emily H. (author)
- VA Puget Sound Health Care System,University of Washington
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- Gryglewski, Gregor (author)
- Medical University of Vienna
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- Lanzenberger, Rupert (author)
- Medical University of Vienna
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- Pijnenburg, Yolande A.L. (author)
- Amsterdam UMC - Vrije Universiteit Amsterdam
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- Barkhof, Frederik (author)
- University College London,Academic Medical Center of University of Amsterdam (AMC)
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- Scheltens, Philip (author)
- Amsterdam UMC - Vrije Universiteit Amsterdam
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- van der Flier, Wiesje M. (author)
- Amsterdam UMC - Vrije Universiteit Amsterdam,Academic Medical Center of University of Amsterdam (AMC)
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- Crane, Paul K. (author)
- University of Washington
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- Ossenkoppele, Rik (author)
- Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Amsterdam UMC - Vrije Universiteit Amsterdam
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(creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
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In: NeuroImage: Clinical. - : Elsevier BV. - 2213-1582. ; 30
- Related links:
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http://dx.doi.org/10... (free)
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https://doi.org/10.1...
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Abstract
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- The clinical presentation of Alzheimer's disease (AD) varies widely across individuals but the neurobiological mechanisms underlying this heterogeneity are largely unknown. Here, we compared regional gray matter (GM) volumes and associated gene expression profiles between cognitively-defined subgroups of amyloid-β positive individuals clinically diagnosed with AD dementia (age: 66 ± 7, 47% male, MMSE: 21 ± 5). All participants underwent neuropsychological assessment with tests covering memory, executive-functioning, language and visuospatial-functioning domains. Subgroup classification was achieved using a psychometric framework that assesses which cognitive domain shows substantial relative impairment compared to the intra-individual average across domains, which yielded the following subgroups in our sample; AD-Memory (n = 41), AD-Executive (n = 117), AD-Language (n = 33), AD-Visuospatial (n = 171). We performed voxel-wise contrasts of GM volumes derived from 3Tesla structural MRI between subgroups and controls (n = 127, age 58 ± 9, 42% male, MMSE 29 ± 1), and observed that differences in regional GM volumes compared to controls closely matched the respective cognitive profiles. Specifically, we detected lower medial temporal lobe GM volumes in AD-Memory, lower fronto-parietal GM volumes in AD-Executive, asymmetric GM volumes in the temporal lobe (left < right) in AD-Language, and lower GM volumes in posterior areas in AD-Visuospatial. In order to examine possible biological drivers of these differences in regional GM volumes, we correlated subgroup-specific regional GM volumes to brain-wide gene expression profiles based on a stereotactic characterization of the transcriptional architecture of the human brain as provided by the Allen human brain atlas. Gene-set enrichment analyses revealed that variations in regional expression of genes involved in processes like mitochondrial respiration and metabolism of proteins were associated with patterns of regional GM volume across multiple subgroups. Other gene expression vs GM volume-associations were only detected in particular subgroups, e.g., genes involved in the cell cycle for AD-Memory, specific sets of genes related to protein metabolism in AD-Language, and genes associated with modification of gene expression in AD-Visuospatial. We conclude that cognitively-defined AD subgroups show neurobiological differences, and distinct biological pathways may be involved in the emergence of these differences.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Alzheimer's disease
- Gene expression
- Gray matter volumes
- Heterogeneity
- Psychometrics
Publication and Content Type
- art (subject category)
- ref (subject category)
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Groot, Colin
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Grothe, Michel J ...
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Mukherjee, Shubh ...
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Jelistratova, Ir ...
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Jansen, Iris
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van Loenhoud, An ...
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Risacher, Shanno ...
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Saykin, Andrew J ...
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Mac Donald, Chri ...
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Mez, Jesse
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Trittschuh, Emil ...
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Gryglewski, Greg ...
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Lanzenberger, Ru ...
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Pijnenburg, Yola ...
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Barkhof, Frederi ...
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Scheltens, Phili ...
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van der Flier, W ...
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Crane, Paul K.
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Ossenkoppele, Ri ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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NeuroImage: Clin ...
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Lund University