The heterogeneity of asymmetric tau distribution is associated with an early age at onset and poor prognosis in Alzheimer’s disease

Jiaying Lu; Zhengwei Zhang; Ping Wu; Xiaoniu Liang; Huiwei Zhang; Jimin Hong; Christoph Clement; Tzu-Chen Yen; Saineng Ding; Min Wang; Zhenxu Xiao; Axel Rominger; Kuangyu Shi; Yihui Guan; Chuantao Zuo; Qianhua Zhao

NeuroImage: Clinical (Jan 2023)

The heterogeneity of asymmetric tau distribution is associated with an early age at onset and poor prognosis in Alzheimer’s disease

Jiaying Lu,
Zhengwei Zhang,
Ping Wu,
Xiaoniu Liang,
Huiwei Zhang,
Jimin Hong,
Christoph Clement,
Tzu-Chen Yen,
Saineng Ding,
Min Wang,
Zhenxu Xiao,
Axel Rominger,
Kuangyu Shi,
Yihui Guan,
Chuantao Zuo,
Qianhua Zhao

Affiliations

Jiaying Lu: Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China; Department of Nuclear Medicine, Inselspital Bern, University Hospital, University of Bern, Bern, Switzerland
Zhengwei Zhang: Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China
Ping Wu: Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China
Xiaoniu Liang: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
Huiwei Zhang: Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China
Jimin Hong: Department of Nuclear Medicine, Inselspital Bern, University Hospital, University of Bern, Bern, Switzerland
Christoph Clement: Department of Nuclear Medicine, Inselspital Bern, University Hospital, University of Bern, Bern, Switzerland
Tzu-Chen Yen: APRINOIA Therapeutics Co., Ltd, Suzhou, China
Saineng Ding: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
Min Wang: Shanghai Institute for Advanced Communication and Data Science, Shanghai University, Shanghai, China; Department of Informatics, Technische Universität München, Munich, Germany
Zhenxu Xiao: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China
Axel Rominger: Department of Nuclear Medicine, Inselspital Bern, University Hospital, University of Bern, Bern, Switzerland
Kuangyu Shi: Department of Nuclear Medicine, Inselspital Bern, University Hospital, University of Bern, Bern, Switzerland; Department of Informatics, Technische Universität München, Munich, Germany
Yihui Guan: Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, China; Corresponding authors at: Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, 518 East Wuzhong Road, Shanghai 200235, China (C. Zuo, Y. Guan); Department of Neurology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China (Q. Zhao).
Chuantao Zuo: Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, China; Corresponding authors at: Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, 518 East Wuzhong Road, Shanghai 200235, China (C. Zuo, Y. Guan); Department of Neurology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China (Q. Zhao).
Qianhua Zhao: Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, China; MOE Frontiers Center for Brain Science, Fudan University, Shanghai, China; Corresponding authors at: Department of Nuclear Medicine & PET Center, Huashan Hospital, Fudan University, 518 East Wuzhong Road, Shanghai 200235, China (C. Zuo, Y. Guan); Department of Neurology, Huashan Hospital, Fudan University, 12 Middle Wulumuqi Road, Shanghai 200040, China (Q. Zhao).

Journal volume & issue: Vol. 38
p. 103416

Abstract

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Purpose: Left-right asymmetry, an important feature of brain development, has been implicated in neurodegenerative diseases, although it’s less discussed in typical Alzheimer’s disease (AD). We sought to investigate whether asymmetric tau deposition plays a potential role in AD heterogeneity. Methods: Two independent cohorts consisting of patients with mild cognitive impairment due to AD and AD dementia with tau PET imaging were enrolled [the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort with 18F-Flortaucipir, the Shanghai Memory Study (SMS) cohort with 18F-Florzolotau]. Based on the absolute global tau interhemispheric differences, each cohort was divided into two groups (asymmetric versus symmetric tau distribution). The two groups were cross-sectionally compared in terms of demographic, cognitive characteristics, and pathological burden. The cognitive decline trajectories were analyzed longitudinally. Results: Fourteen (23.3%) and 42 (48.3%) patients in the ADNI and SMS cohorts showed an asymmetric tau distribution, respectively. An asymmetric tau distribution was associated with an earlier age at disease onset (proportion of early-onset AD: ADNI/SMS/combined cohorts, p = 0.093/0.026/0.001) and more severe pathological burden (i.e., global tau burden: ADNI/SMS cohorts, p < 0.001/= 0.007). And patients with an asymmetric tau distribution were characterized by a steeper cognitive decline longitudinally (i.e., the annual decline of Mini-Mental Status Examination score: ADNI/SMS/combined cohorts, p = 0.053 / 0.035 / < 0.001). Conclusions: Asymmetry in tau deposition, which may be associated with an earlier age at onset, more severe pathological burden, and a steeper cognitive decline, is potentially an important characteristic of AD heterogeneity.

Published in NeuroImage: Clinical

ISSN: 2213-1582 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General): Computer applications to medicine. Medical informatics; Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: http://www.journals.elsevier.com/neuroimage-clinical/

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