Rubisnski et al., in our 2021 Neurobiol Aging paper, assessed the contribution of markers of small vessel disease (SVD), including white matter hyperintensities and cerebral microbleeds, in addition to tau positron emission tomography (tau-PET) and amyloid-PET as predictors of cerebral blood flow (CBF) abnormalities. 

Reduced CBF of the brain tissue is a common pathological alteration in Alzheimer’s disease (AD). Despite CBF alterations being common in AD, their link to primary pathologies, including Aβ and tau, remains unclear. Previously, a correlation between higher Aβ-PET and lower CBF was demonstrated across the spectrum of sporadic AD. Furthermore, brain autopsy studies report that antemortem CBF reduction in AD is related to higher postmortem Braak stages of tau pathology. Given that Aβ deposition is a strong predictor of tau accumulation, any association between tau and CBF may be related to Aβ deposition. Therefore, the main focus of this study was to test whether local tau-PET is associated with lower CBF in spatially corresponding brain regions, with and without controlling for the contribution of A β. 

Furthermore, SVD is common both in aging and AD. Since increased tau-PET levels are also observed in subjects with SVD, the study also assessed to what extent SVD mediates the associations between tau and CBF.

Highlights

• Tau-PET is associated with lower CBF in the entorhinal cortex across the AD continuum.
• The associations between Tau-PET and CBF are independent of Aβ pathology.
• Amyloid-PET is associated with lower CBF in temporoparietal regions.

Rubinski A, Tosun D, Franzmeier N, Neitzel J, Frontzkowski L, Weiner M, Ewers M. Lower cerebral perfusion is associated with tau-PET in the entorhinal cortex across the Alzheimer's continuum. Neurobiol Aging. 2021 Jun;102:111-118. Epub 2021 Feb 10 PubMed.