Microglial activation, but not tau pathology, is independently associated with amyloid positivity and memory impairment

Neurobiol Aging. 2020 Jan:85:11-21. doi: 10.1016/j.neurobiolaging.2019.09.019. Epub 2019 Sep 29.

Abstract

We sought to determine if upstream amyloid accumulation and downstream cognitive impairment have independent relationships with microglial activation and tau pathology. Fifty-eight older adults were stratified by amyloid and cognitive status based on 18F-florbetaben PET, history, and neuropsychological testing. Of these, 57 had 11C-PBR28 PET to measure microglial activation and 43 had 18F-MK-6240 PET to measure tau pathology. Amyloid and cognitive status were associated with increased overall binding for both 11C-PBR28 and 18F-MK-6240 (p's < 0.01). While there was no interaction between amyloid and cognitive status in their association with 11C-PBR28 binding (p = 0.6722), there was an interaction in their association with 18F-MK-6240 binding (p = 0.0115). Binding of both radioligands was greater in amyloid-positive controls than in amyloid-negative controls; however, this difference was seen in neocortical regions for 11C-PBR28 and only in medial temporal cortex for 18F-MK-6240. We conclude that, in the absence of cognitive symptoms, amyloid deposition has a greater association with microglial activation than with tau pathology.

Keywords: Alzheimer's disease; Amyloid; Microglia; Neuroinflammation; Tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / etiology*
  • Amyloid / metabolism*
  • Female
  • Humans
  • Male
  • Memory Disorders / diagnostic imaging
  • Memory Disorders / etiology*
  • Microglia*
  • Middle Aged
  • Positron-Emission Tomography
  • tau Proteins / metabolism

Substances

  • Amyloid
  • tau Proteins