Structural Compression and Entorhinal Vulnerability: Linking Tentorial Adjacency to Tau Burden and Dementia...

Area of Science:

• Neuroscience
• Biomechanical Engineering
• Radiology

Background:

• Alzheimer's disease (AD) is characterized by amyloid-beta plaques and neurofibrillary tangles (NFTs) of tau protein.
• Early tau pathology in the entorhinal cortex (EC) is a key event in AD progression.
• The triggers for initial tau deposition in the EC are not well understood.

Purpose of the Study:

• To test the hypothesis that biomechanical stress from EC-tentorial incisura (TI) proximity initiates tau pathology.
• To investigate EC-TI proximity as a novel risk factor for AD progression.

Main Methods:

• Development of a method to quantify EC-TI proximity using a neuroanatomical contact coefficient (NCC).
• Application of the NCC method to multimodal imaging data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (n=47).
• Stratification of participants into high and low EC-TI adjacency groups and analysis of tau PET signal in relation to cognitive decline and AD conversion.

Main Results:

• High EC-TI proximity was associated with increased risk of AD conversion in individuals with mild cognitive impairment.
• Tau PET signal in the EC predicted conversion to AD exclusively in the high-adjacency group (LLR p=0.009, tau PET in EC p=0.036), even after controlling for other risk factors.
• EC-TI proximity emerged as a significant, anatomically grounded biomarker for AD progression risk.

Conclusions:

• EC-TI proximity represents a novel biomechanical factor contributing to the initiation of tau pathology in sporadic AD.
• This finding suggests a potential role for mechanical stress in AD pathogenesis.
• EC-TI proximity may serve as an early biomarker for AD risk stratification and inform new prevention strategies targeting biomechanical pathways.