Entorhinal vessel density correlates with phosphorylated tau and TDP-43 pathology.

Abstract

The entorhinal cortex (EC) and perirhinal cortex (PC) are vulnerable to Alzheimer's disease. A triggering factor may be the interaction of vascular dysfunction and tau pathology. We imaged post mortem human tissue at 100 μm3 with 7 T magnetic resonance imaging and manually labeled individual blood vessels (mean=270 slices/case). Vessel density was quantified and compared perEC subfield, between EC and PC, and in relation to tau and TAR DNA-binding protein 43 (TDP-43) semiquantitative scores. PC was more vascularized than EC and vessel densities were higher in posterior EC subfields. Tau and TDP-43 strongly correlated with vasculature density and subregions with severe tau at the preclinical stage had significantly greater vessel density than those with low tau burden. These data impact cerebrovascular maps, quantification of subfield vasculature, and correlation of vasculature and pathology at early stages. The ordered association of vessel density, and tau or TDP-43 pathology, may be exploited in a predictive context. Vessel density correlates with phosphorylated tau (p-tau) burden in entorhinal and perirhinal cortices. Perirhinal area 35 and posterior entorhinal cortex showed greatest p-tau burden but also the highest vessel density in the preclinical phase of Alzheimer's disease. We combined an ex vivo magnetic resonance imaging model and histopathology to demonstrate the 3D reconstruction of intracortical vessels and its spatial relationship to the pathology.