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

Background: It has been proposed that amyloid-beta (A beta) 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 A beta 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 C-11-PK11195 PET to measure neuroinflammation levels and C-11-PiB PET to assess A beta 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 A beta deposition. Associations between A beta 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, A beta deposition, as opposed to neuroinflammation, was more associated with cortical atrophy, suggesting a prominent role of A beta in neurodegeneration at a mild stage of the AD.

Automated summary

The study found significant differences in levels of atrophy, neuroinflammation, and A beta deposition between AD patients and healthy controls. Associations between A beta aggregation and brain atrophy were more prominent than those between neuroinflammation and cortical atrophy, indicating a significant role of A beta in neurodegeneration at an early stage of AD.