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Arachnoid Granulation Morphologies Associate with Beta-Amyloid and Tau Pathology in Older Adults

Mehta, R. I.; Wang, T.; Lewis, A.; Walker, C. E.; Gebczak, C.; Barnes, L. L.; Bennett, D. A.; Mehta, R. I.

2025-10-02 pathology
10.1101/2025.09.30.25336940 medRxiv
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INTRODUCTIONArachnoid granulations (AG) enlarge with age, yet limited studies evaluate AG in neurodegeneration. Here, we investigate associations of AG morphology with Alzheimers disease (AD) pathology. METHODSMacroscopic AG properties were systematically evaluated along dorsal postmortem brain specimens from older adults (n=882). Regression models were used to analyze their associations with AD neuropathologic indices, controlling for demographic factors. RESULTSParticipants died at mean age of 90.62 (SD=6.98) years. {beta}-amyloid (Odds ratio/OR, 0.79 [95% CI, 0.66-0.95]) and neurofibrillary tangles (OR, 0.84 [95% CI, 0.71-0.98]) inversely associated with global AG count. Similarly, {beta}-amyloid (OR, 0.78 [95% CI, 0.65-0.92]) and B (Braak) score (OR, 0.80 [95% CI, 0.66-0.96]) inversely associated with global AG patch count. DISCUSSION{beta}-amyloid and tau pathology are associated with AG morphologies. Future studies should explore the mechanisms underlying these associations across disease stage and demographic factors.

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