Network proximity and local tau burden linked to hypoperfusion in Alzheimer's disease

An observational study published in Alzheimer's & Dementia examined how local tau pathology and network proximity to tau-rich regions relate to neuronal dysfunction. Researchers studied 131 amyloid-positive individuals using dynamic [18F]PI-2620 tau positron emission tomography. Kinetic modeling provided distribution volume ratios to assess tau burden and R1 as a perfusion measure. Tau epicenters were defined as the top 10% of regions by distribution volume ratio; connectivity-based distance to these epicenters was calculated using normative resting-state functional connectivity.

At the individual level, hypoperfusion was more closely associated with distance from tau epicenters than with local tau deposition, particularly in early Alzheimer's disease. With advancing biological disease severity, local tau deposition increasingly converged with hypoperfusion. The authors also reported that hypoperfusion mediated the relationship between tau accumulation and cognitive decline. The abstract provides no effect sizes or uncertainty estimates.

The findings suggest that network-dependent remote effects may contribute to dysfunction before local tau burden becomes more closely aligned with perfusion abnormalities. However, these observational associations do not establish causation. Perfusion is an indirect measure of neuronal dysfunction, connectivity estimates were normative rather than individualized, and the unavailable full text limits assessment of methods and clinical applicability.