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

Overview

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.