4.5 Article

Does Microglial Activation Influence Hippocampal Volume and Neuronal Function in Alzheimer's Disease and Parkinson's Disease Dementia?

Journal

JOURNAL OF ALZHEIMERS DISEASE
Volume 51, Issue 4, Pages 1275-1289

Publisher

IOS PRESS
DOI: 10.3233/JAD-150827

Keywords

Alzheimer's disease; neuroinflammation; Parkinson's disease with dementia; PET; volumetric MRI

Categories

Funding

  1. Medical Research Council [G1100810]
  2. National Institute for Health Research (NIHR) Imperial Biomedical Research Centre
  3. Alzheimer's Research UK
  4. Alzheimers Research UK [ART-PG2009-1] Funding Source: researchfish
  5. Medical Research Council [MC_U120036861] Funding Source: researchfish
  6. MRC [G1100810, MC_U120036861] Funding Source: UKRI

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Background: The influence of neuroinflammation on neuronal function and hippocampal atrophy in Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) is still unclear. Objectives: Here we investigated whether microglial activation measured by [C-11]PK11195 PET is associated with neuronal function measured by cerebral glucose metabolic rate (rCMRGlc) using FDG-PET and hippocampal volume measurements. Methods: We enrolled 25 subjects (9 PDD, 8 AD, and 8 controls) who underwent PET scans with [C-11](R)PK11195, [F-18]FDG, and volumetric MRI scanning. Results: SPMcorrelation analysis in AD and PDD showed a negative correlation between hippocampal volume and microglial activation within hippocampus or parahippocampus and with cortical and subcortical areas of projections from hippocampus, while there was a positive correlation between rCMRGlc in cortical and subcortical areas of projections from hippocampus and hippocampal volume. Hippocampal volume was significantly reduced in AD compared to controls but not in PDD. Conclusions: These findings indicate that microglial activation inversely correlated with hippocampal volume and hippocampal rCMRGlc in neurodegenerative diseases with dementia, providing further evidence for the central role of microglial activation in neurodegenerative diseases.

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