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

Area of Science:

• Neuroscience
• Cerebrovascular Biology
• Alzheimer's Disease Research

Background:

• The entorhinal cortex (EC) and perirhinal cortex (PC) are critical for memory and are vulnerable in Alzheimer's disease (AD).
• Vascular dysfunction is increasingly recognized as a contributor to AD pathogenesis, potentially interacting with proteinopathies like tau and TDP-43.

Purpose of the Study:

• To investigate the relationship between cerebral vasculature and neuropathology in the EC and PC.
• To quantify vessel density in specific subfields of the EC and PC and correlate it with tau and TDP-43 pathology in early AD stages.

Main Methods:

• High-resolution (100 μm³) ex vivo 7 Tesla MRI was used to image post-mortem human brain tissue.
• Manual labeling of individual blood vessels was performed across hundreds of slices per case.
• Vessel density was quantified and spatially correlated with semiquantitative scores for tau and TDP-43 pathology.

Main Results:

• The perirhinal cortex (PC) exhibited higher vascularization than the entorhinal cortex (EC).
• Posterior EC subfields showed greater vessel densities compared to anterior regions.
• Significant positive correlations were found between vessel density and both tau and TDP-43 pathology.
• Brain regions with severe tau pathology at preclinical stages had significantly higher vessel density.

Conclusions:

• Vessel density is closely associated with tau and TDP-43 burden in the EC and PC during the preclinical phase of AD.
• Specific areas like perirhinal area 35 and posterior EC demonstrate high p-tau and vessel density.
• The spatial relationship between vasculature and pathology suggests potential for predictive models in early AD detection.