Lower cerebral perfusion is associated with tau-PET in the entorhinal cortex across the Alzheimer's continuum

Alzheimer's disease (AD) is associated with reduced temporo-parietal cerebral blood flow (CBF). However, a substantial variability in CBF across the clinical spectrum of AD has been reported, possibly due to differences in primary AD pathologies. Here, we assessed CBF (ASL-MRI), tau (AV1451-PET) and amyloid (AV45/FBB-PET) in 156 subjects across the AD continuum. Using mixed-effect regression analyses, we assessed the local associations between amyloid-PET, tau-PET and CBF in a hypothesis-driven way focusing on each pathology's predilection areas. The contribution of Apolipoprotein E (APOE) genotype, and MRI markers of small vessel disease (SVD) to alterations in CBF were assessed as well. Tau-PET was associated with lower CBF in the entorhinal cortex, independent of Aβ. Amyloid-PET was associated with lower CBF in temporo-parietal regions. No associations between MRI markers of SVD and CBF were observed. These results provide evidence that in addition to Aβ, pathologic tau is a major correlate of CBF in early Braak stages, independent of Aβ, APOE genotype and SVD markers.