Abstract #0755

The relationship between tau protein and white matter structural changes in Alzheimer's disease using fixel-based analysis

Takafumi Kitagawa¹, Koji Kamagata¹, Wataru Uchida^1,2, Kaito Takabayashi¹, Christina Andica^1,2, Rui Zou¹, Takuya Ozawa¹, Akifumi Hagiwara¹, Toshiaki Akashi¹, Katsuhiro Sano¹, Akihiko Wada¹, and Shigeki Aoki^1,2

¹Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan, ²Faculty of Health Data Science, Juntendo University, Chiba, Japan

Synopsis

Keywords: Alzheimer's Disease, Alzheimer's Disease

Motivation: Studies have suggested that tau deposition induced neurotoxicity causes progressive white matter degeneration in Alzheimer's disease; however, this has not yet been fully elucidated.

Goal(s): To assess tau-related white matter (WM) degeneration in the whole brain and its effects on cognitive function using fixel-based analysis (FBA).

Approach: WM integrity and cortical tau load were compared in Alzheimer's disease, mild cognitive impairment, and cognitive normal subjects using FBA and ¹⁸F-flortaucipir.

Results: FBA metrics in subcortical WM of highly tau-deposited cortex showed degeneration of both micro and macrostructures. An association between entorhinal tau and cognitive function was mediated by FBA metrics in entorhinal subcortical WM.

Impact: Our findings suggest the possibility that neurons were degenerated through the propagation of tau along the WM and may shed light on future research on the mechanisms of cognitive decline in Alzheimer's disease.

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