Quantitative Assessment of Hippocampal Tau Pathology in AD and PART

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Quantitative Assessment of Hippocampal Tau Pathology in AD and PART Lei Zhang 1,2 & Yankai Jiang 3 & Jie Zhu 4 & Huazheng Liang 5 & Xiangyang He 3 & Jiahong Qian 3 & Hai Lin 3 & Yubo Tao 3 & Keqing Zhu 1,2 Received: 6 November 2019 / Accepted: 23 April 2020 # The Author(s) 2020

Abstract To quantitatively assess the distribution pattern of hippocampal tau pathology in Alzheimer’s disease (AD) and primary agerelated tauopathy (PART), we investigated the distribution of phosphorylated tau protein (AT8) in 6 anatomically defined subregions of the hippocampal formation and developed a mathematical algorithm to compare the patterns of tau deposition in PART and AD. We demonstrated regional patterns of selective vulnerability as distinguishing features of PART and AD in functionally relevant structures of the hippocampus. In AD cases, tau pathology was high in both CA1 and subiculum, followed by CA2/3, entorhinal cortex (EC), CA4, and dentate gyrus (DG). In PART, the severity of tau pathology in CA1 and subiculum was high, followed by EC, CA2/3, CA4, and DG. There are significant differences between sector DG and CA1, DG and subiculum in both AD and PART. Keywords Hippocampus . Tau pathology . Alzheimer’s disease . Primary age-related tauopathy

Primary age-related tauopathy (PART) is defined recently by the presence of Alzheimer’s disease (AD)-type neurofibrillary changes without or with few Aβ plaques. The working classification for definite PART is based on the presence of neurofibrillary tangle (NFT) along with Braak stage ≤ IVand Thal Lei Zhang and Yankai Jiang contributed equally to this work. * Yubo Tao [email protected] * Keqing Zhu [email protected] 1

China Brain Bank and Department of Neurology in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, and Department of Neurobiology, Zhejiang University School of Medicine, 866 Yu Hang Tang Road, Hangzhou 310058, China

2

Department of Pathology, Zhejiang University School of Medicine, Hangzhou 310058, China

3

State Key Lab of CAD&CG, College of Computer Science and Technology, Zhejiang University, 866 Yu Hang Tang Road, Hangzhou 310058, China

4

Zhejiang University School of Medicine, Hangzhou 310058, China

5

Department of Neurology, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, China

Aβ phase as 0 (Crary et al. 2014). It remains a debate whether PART is a subtype of AD or a distinct tauopathy different from AD (Duyckaerts et al. 2015; Jellinger et al. 2015). How to differentiate PART from AD is an important issue to solve. The hippocampus is an early region demonstrating tau pathology in both PART and AD. A recent study has indicated differences in the pattern of hippocampal tau pathology between classical AD and PART (Crary et al. 2014). Retrospective semiquantitative assessment of tau pathology in hippocampal subregions indicated more severe involvement in CA2 in PART cases than other region