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The Role of TDP-43 in Alzheimer’s Disease

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Abstract

The transactive response DNA binding protein (TDP-43) has long been characterized as a main hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U, also known as FTLD-TDP). Several studies have indicated TDP-43 deposits in Alzheimer’s disease (AD) brains and have robust connection with AD clinical phenotype. FTLD-U, which was symptomatically connected with AD, may be predictable for the comprehension of the role TDP-43 in AD. TDP-43 may contribute to AD through both β-amyloid (Aβ)-dependent and Aβ-independent pathways. In this article, we summarize the latest studies concerning the role of TDP-43 in AD and explore TDP-43 modulation as a potential therapeutic strategy for AD. However, to date, little of pieces of the research on TDP-43 have been performed to investigate the role in AD; more investigations need to be confirmed in the future.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81471309, 81371406, and 81171209), the Shandong Provincial Outstanding Medical Academic Professional Program, Qingdao Key Health Discipline Development Fund, Qingdao Outstanding Health Professional Development Fund, and Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders.

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The authors declare no conflicts of interest.

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    Authors and Affiliations

    1. Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, China

      Xiao-Long Chang & Lan Tan

    2. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China

      Meng-Shan Tan, Lan Tan & Jin-Tai Yu

    3. Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, USA

      Jin-Tai Yu

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    1. Xiao-Long Chang
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    2. Meng-Shan Tan
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    3. Lan Tan
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    Correspondence to Lan Tan or Jin-Tai Yu.

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    X. L. Chang and M. S. Tan are co-first authors.

    Xiao-Long Chang and Meng-Shan Tan contributed equally to this work.

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    Chang, XL., Tan, MS., Tan, L. et al. The Role of TDP-43 in Alzheimer’s Disease. Mol Neurobiol 53, 3349–3359 (2016). https://doi.org/10.1007/s12035-015-9264-5

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