Investigating the Spatial Associations Between Amyloid-ß Deposition, Grey Matter Volume, and Neuroinflammation in Alzheimer's Disease.

ABSTRACT

BACKGROUND: It has been proposed that amyloid-ß (Aß) plays a causal role in Alzheimer's disease (AD) by triggering a series of pathologic events-possibly including neuroinflammation-which culminate in progressive brain atrophy. However, the interplay between the two pathological molecular events and how both are associated with neurodegeneration is still unclear. OBJECTIVE: We aimed to estimate the spatial inter-relationship between neurodegeneration, neuroinflammation and Aß deposition in a cohort of 20 mild AD patients and 17 healthy controls (HC). METHODS: We resorted to magnetic resonance imaging to measure cortical atrophy, using the radiotracer 11C-PK11195 PET to measure neuroinflammation levels and 11C-PiB PET to assess Aß levels. Between-group comparisons were computed to explore AD-related changes in the three types of markers. To examine the effects of each one of the molecular pathologic mechanisms on neurodegeneration we computed 1) ANCOVAs with the anatomic data, controlling for radiotracer uptake differences between groups and 2) voxel-based multiple regression analysis between-modalities. In addition, associations in anatomically defined regions of interests were also investigated. RESULTS: We found significant differences between AD and controls in the levels of atrophy, neuroinflammation, and Aß deposition. Associations between Aß aggregation and brain atrophy were detected in AD in a widely distributed pattern, whereas associations between microglia activation and structural measures of neurodegeneration were restricted to few anatomically regions. CONCLUSION: In summary, Aß deposition, as opposed to neuroinflammation, was more associated with cortical atrophy, suggesting a prominent role of Aß in neurodegeneration at a mild stage of the AD.