Microglial responses partially mediate the effect of Aβ on cognition in Alzheimer's disease

INTRODUCTION: Microglial responses are an integral part of Alzheimer's disease (AD) pathology and are associated with amyloid beta (A beta) deposition. This study aimed to investigate the effects of A beta and microglial responses on global cognitive impairment. METHODS: In this longitudinal study, 28 patients with mild cognitive impairment and 11 healthy controls underwent C-11-PK11195 and C-11-Pittsburgh compound B positron emission tomography (PET), structural magnetic resonance imaging scans, and global cognitive ratings at baseline and 2-year follow-up. Correlations between PET uptake and global cognition were assessed. Additionally, the mediation effect of the microglial response on the association between A beta load and global cognition was assessed. RESULTS: A beta load and the microglial response were both independently detrimental to global cognitive performance at baseline; however, at 2-year follow-up the association between A beta load and global cognitive ratings was partially mediated by the microglial response. DISCUSSION: As AD progresses, the associated microglial response partially mediates the detrimental effect of aggregated A beta on cognition.