Abstract #3912

Evaluation of the relation between tau protein and white matter structural changes in Alzheimer's disease using fixel-based analysis

Takafumi Kitagawa^1,2, Koji Kamagata¹, Wataru Uchida¹, Keigo Yamazaki^1,3, Kaito Takabayashi¹, Yuya Saito¹, Christina Andica^1,4, Akifumi Hagiwara¹, Toshiaki Akashi¹, Katsuhiro Sano¹, Akihiko Wada¹, and Shigeki Aoki^1,2,4

¹Department of Radiology, Juntendo University Graduate School of Medicine, Tokyo, Japan, ²Department of Data Science, Juntendo University Graduate School of Medicine, Tokyo, Japan, ³Department of Radiological Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan, ⁴Faculty 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 (WM) degeneration in Alzheimer's disease (AD) and its prodromal phase; however, this is not yet fully elucidated.

Goal(s): To employ fixel-based analysis (FBA) to assess tau-related WM degeneration and its effect to cognitive function.

Approach: The WM integrity and cortical tau load were compared across AD, mild cognitive impairment, and cognitive normal subjects using FBA and tau PET.

Results: FBA metrics in WM under highly tau-deposited cortex were downward with higher effect sizes in patients. An association between entorhinal tau and cognitive function was mediated by FBA metrics in the parahippocampal cingulum.

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

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