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The Protective A673T Mutation of Amyloid Precursor Protein (APP) in Alzheimer’s Disease

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Abstract

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by extracellular amyloid beta peptides and neurofibrillary tangles consisted of intracellular hyperphosphorylated Tau in the hippocampus and cerebral cortex. Most of the mutations in key genes that code for amyloid precursor protein can lead to significant accumulation of these peptides in the brain and cause Alzheimer’s disease. Moreover, some point mutations in amyloid precursor protein can cause familial Alzheimer’s disease, such as Swedish mutation (KM670/671NL) and A673V mutation. However, recent studies have found that the A673T mutation in amyloid precursor protein gene can protect against Alzheimer’s disease, even if it is located next to the Swedish mutation (KM670/671NL) and at the same site as A673V mutation, which are pathogenic. It makes us curious about the protective A673T mutation. Here, we summarize the most recent insights of A673T mutation, focus on their roles in protective mechanisms against Alzheimer’s disease, and discuss their involvement in future treatment.

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Acknowledgements

We would like to thank our supporters: National Natural Science Foundation of China (81701078, 81773165), Natural Science Foundation of Heilongjiang Province of China (QC2017090), University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (UNPYSCT-2016190), China Postdoctoral Science Foundation (2016M600261, 2018T110317), The Innovative Science Research Project of Harbin Medical University (2016JCZX37), Heilongjiang Postdoctoral Financial Assistance (LBH-Z15163), and Heilongjiang Touyan Innovation Team Program.

Funding

This work was supported in part by grants from the National Natural Science Foundation of China (81701078, 81773165), Natural Science Foundation of Heilongjiang Province of China (QC2017090), University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (UNPYSCT-2016190), China Postdoctoral Science Foundation (2016M600261, 2018T110317), The Innovative Science Research Project of Harbin Medical University (2016JCZX37), Heilongjiang Postdoctoral Financial Assistance (LBH-Z15163), and Heilongjiang Touyan Innovation Team Program.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China

    Qing Xia, XinYu Yang, JiaBin Shi, ZiJie Liu, YaHui Peng, WenJing Wang, BoWen Li, Yu Zhao, JiaYing Xiao, Lei Huang, DaYong Wang & Xu Gao

  2. Basic Medical Institute, Heilongjiang Medical Science Academy, Harbin, China

    YaHui Peng, DaYong Wang & Xu Gao

  3. Translational Medicine Center of Northern China, Harbin, China

    YaHui Peng, DaYong Wang & Xu Gao

  4. Key Laboratory of Heilongjiang Province for Genetically Modified Animals, Harbin Medical University, Harbin, China

    YaHui Peng, DaYong Wang & Xu Gao

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  1. Qing Xia
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All authors contributed to the article. Xu Gao and DaYong Wang had the idea for the article. The first draft of the manuscript was written by Qing Xia, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to DaYong Wang or Xu Gao.

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Xia, Q., Yang, X., Shi, J. et al. The Protective A673T Mutation of Amyloid Precursor Protein (APP) in Alzheimer’s Disease. Mol Neurobiol 58, 4038–4050 (2021). https://doi.org/10.1007/s12035-021-02385-y

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