タウ蛋白質の沈着パターンでアルツハイマー病の重症度が予測される(Tau protein deposition patterns predict Alzheimer’s severity)

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2024-05-15 ワシントン大学セントルイス校

セントルイスのワシントン大学医学部の研究者たちは、脳スキャンのタウ病理パターンを分析することでアルツハイマー病の進行度を評価する方法を開発しました。この方法は、個々の患者における病気の進行度を把握し、治療の決定に役立つ可能性があります。タウタンパク質の蓄積と拡散はアルツハイマー病の主要な病理過程であり、研究チームは機械学習を用いて患者の脳スキャンデータを分析し、臨床的および認知的な結果と相関する8つのタウ沈着パターンを特定しました。これにより、タウ沈着パターンとアルツハイマー病の重症度を結びつけるモデルが作成されました。この研究は『Alzheimer’s and Dementia』誌に掲載されています。

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アルツハイマー病におけるフロルタウシピル取り込みのデータ駆動型分解とステージング Data-driven decomposition and staging of flortaucipir uptake in Alzheimer’s disease

Tom Earnest, Abdalla Bani, Sung Min Ha, Diana A. Hobbs, Deydeep Kothapalli, Braden Yang, John J. Lee, Tammie L. S. Benzinger, Brian A. Gordon, Aristeidis Sotiras, for the Alzheimer’s Disease Neuroimaging Initiative …
Alzheimer’s & Dementia  Published: 29 April 2024
DOI:https://doi.org/10.1002/alz.13769

Details are in the caption following the image

Abstract

INTRODUCTION
Previous approaches pursuing in vivo staging of tau pathology in Alzheimer’s disease (AD) have typically relied on neuropathologically defined criteria. In using predefined systems, these studies may miss spatial deposition patterns which are informative of disease progression.

METHODS
We selected discovery (n = 418) and replication (n = 132) cohorts with flortaucipir imaging. Non-negative matrix factorization (NMF) was applied to learn tau covariance patterns and develop a tau staging system. Flortaucipir components were also validated by comparison with amyloid burden, gray matter loss, and the expression of AD-related genes.

RESULTS
We found eight flortaucipir covariance patterns which were reproducible and overlapped with relevant gene expression maps. Tau stages were associated with AD severity as indexed by dementia status and neuropsychological performance. Comparisons of flortaucipir uptake with amyloid and atrophy also supported our model of tau progression.

DISCUSSION
Data-driven decomposition of flortaucipir uptake provides a novel framework for tau staging which complements existing systems.

Highlights

  • NMF reveals patterns of tau deposition in AD.
  • Data-driven staging of flortaucipir tracks AD severity.
  • Learned flortaucipir patterns overlap with AD-related gene expression.
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