09/11/2025
✨ VERY EXCITED to share groundbreaking research by John Crary, Frank Provenzano, et al. ✨
(AD) is a growing public health crisis. This is the first study to examine what triggers tau pathology in , rather than just tracking its progression.
Alzheimers disease is defined neuropathologically by the accumulation of amyloid-β plaques and neurofibrillary tangles (NFTs) composed of abnormal tau protein in the brain.
Early neurofibrillary degeneration in the entorhinal cortex (EC) is a hallmark of AD and a critical initiating event in the hierarchical pathoanatomical progression. However, the factors triggering initial tau deposition in the EC remain unclear.
Here, John Crary, Frank Provenzano, et al. propose a novel biomechanical cascade hypothesis, positing that the unique anatomical inferomedial positioning of the EC, including proximity to the tentorial incisura (TI) and other skull base structures, renders it susceptible to very mild yet persistent age-related mechanical stress, analogous to the effects of repetitive mild , triggering tau pathology.
Their findings identify EC-TI proximity as a novel and anatomically grounded biomarker of AD progression risk. More broadly, they suggest a previously unrecognized biomechanical contribution to the initiation of tau pathology in aging and sporadic AD, opening new avenues for early detection, risk stratification, and mechanistically targeted prevention strategies.
Learn More in BioRxiv
https://www.biorxiv.org/content/10.1101/2025.09.02.670249v1.full
Structural Compression and Entorhinal Vulnerability: Linking Tentorial Adjacency to Tau Burden and Dementia Progression
- Luyue Zhang, Ana M. Franceschi, John Crary, Frank Provenzano, the Alzheimer’s Disease Neuroimaging Initiative
Icahn School of Medicine at Mount Sinai The Mount Sinai Hospital Windreich Department of Artificial Intelligence and Human Health, Mount Sinai Department of Pathology, Neuropathology Brain Bank & Research CoRE, Ronald M. Loeb Center for Alzheimer’s Disease Graduate School of Biomedical Sciences at the Icahn School of Medicine Columbia University Columbia University Irving Medical Center Donald & Barbara Zucker School of Medicine
Image courtesy of Jill K. Gregory, MFA, CMI
