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

J Alzheimers Dis. 2016;51(4):1275-89. doi: 10.3233/JAD-150827.

Abstract

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 [11C]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 [11C](R)PK11195, [18F]FDG, and volumetric MRI scanning.

Results: SPM correlation 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.

Keywords: Alzheimer’s disease; PET; Parkinson’s disease with dementia; neuroinflammation; volumetric MRI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology*
  • Antineoplastic Agents / pharmacokinetics
  • Brain Mapping
  • Cognition
  • Female
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Hippocampus / diagnostic imaging
  • Hippocampus / drug effects
  • Hippocampus / pathology*
  • Humans
  • Isoquinolines / pharmacokinetics
  • Magnetic Resonance Imaging
  • Male
  • Microglia / drug effects
  • Microglia / metabolism
  • Microglia / pathology*
  • Middle Aged
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology*
  • Neuropsychological Tests
  • Parkinson Disease / diagnostic imaging
  • Parkinson Disease / pathology*
  • Positron-Emission Tomography
  • Psychiatric Status Rating Scales
  • Supranuclear Palsy, Progressive / diagnostic imaging
  • Supranuclear Palsy, Progressive / pathology*

Substances

  • Antineoplastic Agents
  • Isoquinolines
  • Fluorodeoxyglucose F18
  • PK 11195

Supplementary concepts

  • Progressive supranuclear palsy atypical