Relationships Between Tau and Glucose Metabolism Reflect Alzheimer’s Disease Pathology in Cognitively Normal Older Adults

Tau is associated with hypometabolism in patients with Alzheimer’s disease. In normal aging, the association between tau and glucose metabolism is not fully characterized. We used [18F] AV-1451, [18F] Fluorodeoxyglucose, and [11C] Pittsburgh Compound-B (PiB) PET to measure associations between tau and glucose metabolism in cognitively normal older adults (N = 49). Participants were divided into amyloid-negative (PiB–, n = 28) and amyloid-positive (PiB+, n = 21) groups to determine effects of amyloid-β. We assessed both local and across-brain regional tau–glucose metabolism associations separately in PiB–/PiB+ groups using correlation matrices and sparse canonical correlations. Relationships between tau and glucose metabolism differed by amyloid status, and were primarily spatially distinct. In PiB– subjects, tau was associated with broad regions of increased glucose metabolism. In PiB+ subjects, medial temporal lobe tau was associated with widespread hypometabolism, while tau outside of the medial temporal lobe was associated with decreased and increased glucose metabolism. We further found that regions with earlier tau spread were associated with stronger negative correlations with glucose metabolism. Our findings indicate that in normal aging, low levels of tau are associated with a phase of increased metabolism, while high levels of tau in the presence of amyloid-β are associated with hypometabolism at downstream sites.