Functional Correlates of Microglial and Astrocytic Activity in Symptomatic Sporadic Alzheimer's Disease: A CSF/18F-FDG-PET Study.

ABSTRACT

Glial and microglial cells contribute to brain glucose consumption and could actively participate in shaping patterns of brain hypometabolism. Here, we aimed to investigate the association between 18F-fluorodeoxyglucose (18F-FDG) uptake and markers of microglial and astrocytic activity in a cohort of patients with Alzheimer's Disease (AD). We dosed cerebrospinal fluid (CSF) levels of soluble Triggering Receptor Expressed on Myeloid cells (sTREM2), Glial Fibrillary Acidic Protein (GFAP), a marker of reactive astrogliosis, and ß-S100, a calcium-binding protein associated with a neurotoxic astrocytic profile. No associations were found between sTREM-2 and 18F-FDG uptake. Instead, 18F-FDG uptake was associated negatively with CSF ß-S100 in the left supramarginal gyrus, inferior parietal lobe and middle temporal gyrus (Brodmann Areas (BA) 21 and 40). Increased ß-S100 levels could negatively regulate neuronal activity in the temporo-parietal cortex to prevent damage associated with AD hyperactivity, or rather they could reflect neurotoxic astrocytic activation contributing to AD progression in key strategic areas. We also identified a trend of positive association of 18F-FDG uptake with CSF GFAP in the right fronto-medial and precentral gyri (BA 6, 9 and 11), which has been reported in early AD and could either be persisting as an epiphenomenon tied to disease progression or be specifically aimed at preserving functions in the frontal cortex. Overall, CSF markers of astrogliosis seem to correlate with cortical glucose uptake in symptomatic sporadic AD, highlighting the role of astrocytes in shaping regional hypometabolism and possibly clinical presentation.