Influence of microglial activation on neuronal metabolism in Alzheimer’s disease: A hybrid 3D-MRSI/PET study

Motivation: To understand the influence of microglial activation on neuronal metabolism across prodromal AD and AD dementia stages. Goal(s): To investigate the whole-brain relationship between microglial activation and neuronal metabolism at regional and voxel levels. Approach: A combined [18F]DPA-714 PET and 3D-MRSI (resolution: 2×3×3 mm3) was used to simultaneously map whole-brain levels of N-acetylaspartate and microglial activation in cognitively normal (CN), prodromal AD and AD dementia patients. Results: Correlations between microglial activation and N-acetylaspartate shift markedly, from predominantly positive in parietal and anterior cingulate cortices in CN to predominantly negative in frontal and temporal cortices in AD. Impact: Using a hybrid 3D-MRSI/PET approach, we identified a biphasic effect of microglial activation on neuronal metabolism across healthy, prodromal AD and AD dementia stages. This approach provides a valuable tool for evaluating neuroinflammation and neuronal integrity throughout AD progression.