Dataset Information

Metabolic regional and network changes in Alzheimer's disease subtypes.

ABSTRACT: Clinical variants of Alzheimer's disease (AD) include the common amnestic subtype as well as subtypes characterised by leading visual processing impairments or by multimodal neurocognitive deficits. We investigated regional metabolic patterns and networks between AD subtypes. The study comprised 9 age-matched controls and 25 patients with mild to moderate AD. Methods included clinical and neuropsychological assessment, high-resolution FDG PET and T1-weighted 3D MR imaging with PET-MR coregistration, grey matter segmentation, atlas-based regions-of-interest, linear mixed effects and regional correlation analysis. Regional metabolic patterns differed significantly between groups, but significant hypometabolism in the posterior cingulate cortex (PCC) was common to all subtypes. The most distinctive regional abnormality was occipital hypometabolism in the visual subtype. In controls, two large clusters of positive regional metabolic correlations were observed. The most pronounced breakdown of the normal correlation pattern was found in amnestic patients who, in contrast, showed the least regional focal metabolic deficits. The normal positive correlation between PCC and hippocampus was lost in all subtypes. In conclusion, PCC hypometabolism and metabolic correlation breakdown between PCC and hippocampus are the common functional core of all AD subtypes. Network alterations exceed focal regional impairment and are most prominent in the amnestic subtype.

SUBMITTER: Herholz K

PROVIDER: S-EPMC6168902 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Metabolic regional and network changes in Alzheimer's disease subtypes.

Herholz Karl K Haense Cathleen C Gerhard Alex A Jones Matthew M Anton-Rodriguez José J Segobin Shailendra S Snowden Julie S JS Thompson Jennifer C JC Kobylecki Christopher C

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20170704 10

Clinical variants of Alzheimer's disease (AD) include the common amnestic subtype as well as subtypes characterised by leading visual processing impairments or by multimodal neurocognitive deficits. We investigated regional metabolic patterns and networks between AD subtypes. The study comprised 9 age-matched controls and 25 patients with mild to moderate AD. Methods included clinical and neuropsychological assessment, high-resolution FDG PET and T1-weighted 3D MR imaging with PET-MR coregistrat ...[more]

PMID: 28675110

Similar Datasets

Project description:Along with the two hallmark pathologies—intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques—transcriptional studies suggest that Alzheimer's disease (AD) results from dysfunction of many cellular pathways including synaptic transmission, cytoskeletal dynamics, and apoptosis. While these studies consistently point to the same pathways involved in AD, there is no consensus on which genes in each pathway are disease-relevant, much less on whether these genes play causative roles or are downstream effects of disease progression. To address these issues, we have performed a large-scale transcriptional analysis in brain of individuals with advanced AD and non-demented controls, focusing specifically on CA1 and the relatively less affected CA3. For comparisons between regions and across disease status, we find consistency in both pathway enrichment as well as specific differentially expressed genes across several studies. Furthermore, genes that show decreased expression with AD progression also tend to show enrichment in CA3 (and vice versa), suggesting that transcription levels in a region may reflect that region's vulnerability to disease. In particular, we find several strong candidate vulnerability (ABCA1, MT1H, PDK4, RHOBTB3) and protection (FAM13A1, LINGO2, UNC13C) genes based on expression patterns. We have also applied weighted gene coexpression network analysis (WGCNA) to explore the pathophysiology of AD from a systems perspective, finding modules for major cell types, which each show distinct disease-relevant expression patterns. In particular, a microglial module shows increased expression in the brain of non-demented controls harboring early NFT pathology, suggesting that microglial activation is an early event in AD progression. Total RNA obtained from 60um sections of frozen human hippocampus was collected using scalpel dissection. Control and AD brains were matched for all non-disease characteristics as closely as possible. CA1 and CA3 dissections for a given individual were taken from the same section. Several region- and disease-related comparisons were performed.

Dataset Information

Metabolic regional and network changes in Alzheimer's disease subtypes.

Publications

Metabolic regional and network changes in Alzheimer's disease subtypes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets