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Abstract
Background: We aimed to investigate the clinical correlates of principal components (PCs) of tau positron emission tomography (PET) and their predictability for longitudinal changes in tau accumulation in Alzheimer's disease (AD).

Methods: We enrolled 272 participants who underwent two PET scans [18F-flortaucipir for tau and 18F-florbetaben for amyloid-β (Aβ)], brain magnetic resonance imaging, and neuropsychological tests as baseline assessments. Among them, 187 participants underwent the same follow-up assessments after an average of 2 years. Using Aβ-positive AD dementia-specific PCs obtained from the baseline scans of 56 Aβ-positive patients with AD dementia, we determined the expression of the first two PCs (PC1 and PC2) in all participants. We assessed the correlation of PC expression with baseline clinical characteristics and tau accumulation rates. Moreover, we investigated the predictability of PCs for the longitudinal tau accumulation in training and test sets.

Results: PC1 corresponded to the tau distribution pattern in AD, while the two PC2 extremes reflected the parietal or temporal predominance of tau distribution. PC1 expression increased with tau burden and decreased with cognitive impairment, while PC2 expression decreased with advanced age and visuospatial and attention function deterioration. The tau accumulation rate was positively correlated with PC1 expression (greater tau burden) and negatively correlated with PC2 expression (temporal predominance). A regression model using both PCs could predict longitudinal changes in the tau burden (intraclass correlation coefficient = 0.775, R2 = 0.456 in test set).

Conclusions: PC analysis of tau PET could be useful for evaluating disease progression, characterizing the tau distribution pattern, and predicting longitudinal tau accumulation.

베타아밀로이드양성 알츠하이머 치매 양상 PCs 타우 PET의 Voxel-wise maps 과 group-wise averaged 타우 PET 영상.

Individual PC1 score는 전체 대뇌피질의 타우 섭취와 상관관계를 가졌고 PC1 score의 증가에 따라 대뇌피질의 타우 침착량이 증가하였다. Individual PC2 score는 prefrontal, parietal, occipital, and posterior cingulate 피질 영역의 타우 섭취와 상관관계를 가졌고 낮은 PC2 양상을 보인 그룹에서는 주로 측두엽에, 높은 PC2 양상을 보인 그룹에서는 두정엽에 주로 분포양상을 보였다.

Affiliations

Hanna Cho  1 , Min Seok Baek  1 , Hye Sun Lee  2 , Jae Hoon Lee  3 , Young Hoon Ryu  4 , Chul Hyoung Lyoo  5
1 Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, 20 Eonjuro 63-gil, Gangnam-gu, Seoul, South Korea.
2 Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, South Korea.
3 Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul, South Korea.
4 Department of Nuclear Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211 Eonjuro, Gangnam-gu, Seoul, South Korea. ryuyh@yuhs.ac.
5 Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, 20 Eonjuro 63-gil, Gangnam-gu, Seoul, South Korea. lyoochel@yuhs.ac.