HAI Book 2025 - Flipbook - Page 412
Provenzano, Frank
102
Mechanical stress of the entorhinal cortex: A potential driver of tau
pathology?
Luyue Zhang1, John Crary2, Frank Provenzano1
1
Columbia University, New York, NY, US
Ichan School of Medicine, New York, NY, US
2
Introduction: Taupathic changes, namely neurofibrillary tangle deposition in the temporal lobe, are a hallmark of
Alzheimer's disease (AD). Tangle deposition is associated with multiple neurodegenerative conditions, as well as
traumatic brain injury (TBI). There are several intrinsic mechanisms that have been suggested to initiate the
spread of tau in Alzheimer9s disease, however less is known about external or structural contributions, specifically
in the entorhinal cortex where tau is first shown to accumulate.
Methods: In a cohort of 47 MCI individuals with structural MRI and Tau PET who do (n=24) and do not (n=23) go on
to convert to AD, we develop a metric for measuring the proximity between the entorhinal cortex (EC) and
tentorial incisor. We do so using FreeSurfer and manual ROIs and then model the volume of this channel using a
space index. We then heuristically divide the groups using a threshold of the space index into close and distant
proximity. We then test relationships between the proximity measure, conversion and tau PET entorhinal cortex
SUVr.
Results: We discovered a significant relationship between entorhinal tau PET and conversion, agnostic of amyloid
status, in the close-proximity group (p=0.017), but not in the-proximity group (p=0.467). Proximity measure was
not correlated with conversion, tau EC SUVr, nor entorhinal or hippocampal volume.
Discussion: The data presented in a well-characterized cohort with structural imaging and measures of regional
tau uptake suggest a possible relationship between the closeness of the entorhinal cortex with a stiff structure
medial to it that may be a source of repeated compressive action. This measure can be applied to any reasonable
quality structural MRI scan and posits a potential physical mechanism and source of tau deposition. This suggests
a potential chronic cause of tau deposition and AD risk.
HAI2025 - 412
