Plasma p-tau217 and glucose metabolism correlate in association neocortical areas in Alzheimer's disease

Abstract While the biomarkers available for Alzheimer's disease are continually expanding, including clinically approved blood tests, not all of the relationships between various biomarkers have been fully elucidated. In this study, we explore how regional brain metabolism, as measured by fludeoxyglucose-18 (FDG)-PET, relates to plasma biomarkers such as p-tau217, Glial fibrillary acidic protein (GFAP), phosphorylated-tau (p-tau)217/beta-amyloid (Aβ) 42, and Aβ42/40 in a cohort of participants with early symptomatic Alzheimer’s disease. P-tau217 showed a consistent pattern of participants with higher p-tau217 levels having increased hypometabolism in Alzheimer’s disease-related regions in association neocortical areas such as the lateral temporal cortex, the precuneus and inferior parietal cortex and atrophy accompanied by greater cognitive impairment. GFAP also related to regional hypometabolism and atrophy in regions known to be affected in Alzheimer’s disease, though with a slightly different regional pattern. We additionally observed that participants with equivalent biomarker levels still exhibited diverse patterns of FDG-PET and atrophy. This suggests that, despite the above correlations, imaging provides additional information. These findings support and extend our knowledge of how plasma p-tau217 relates to other Alzheimer’s disease biomarkers and cerebral metabolism, helping to contextualize both the benefits and limitations of these plasma biomarkers.