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Spreading of Pathology in Alzheimer’s Disease

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Abstract

The senile plaques (SPs) and neurofibrillary tangles (NFTs) are the two major pathological hallmarks of AD, which are composed of β-amyloid protein and Tau protein. So the β-amyloid protein (Aβ) and Tau oligomers (oTau) are the majority in the pathology of AD. Recently, the spreading of Aβ and oTau in the brain of AD patients has received heated value. In this review, we summarize recent research progress and aim to figure out the spreading mechanism of Aβ and Tau in AD via introduction of the formation, release, uptake, diffusion between different brain regions, and the propagation principle of Aβ and Tau. Although the mechanisms of the spreading pathology in AD are still not very clear, increasing discoveries confirm that Aβ and oTau could transmit from one neuron to another along the anatomical connected synapses. Meanwhile, a mass of studies also report that they have a totally opposite hierarchical spatiotemporal pattern of spreading in cerebral areas. In addition, Tau proteins might mediate Aβ toxicity in the brain, and they might have synergistic roles with each other. So some therapies have emerged, such as inhibiting the release, preventing the oligomerization, and blocking the uptake. This review would be helpful to comprehend the mechanism of transmission in AD and provide a new way to the targeted therapy.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81471309, 81571245, and 81501103), the Shandong Taishan Scholar, Qingdao Key Health Discipline Development Fund, and Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders.

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Authors and Affiliations

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

    Zhong-Yue Lv & Lan Tan

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

    Chen-Chen Tan, Jin-Tai Yu & Lan Tan

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  1. Zhong-Yue Lv
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  2. Chen-Chen Tan
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  3. Jin-Tai Yu
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  4. Lan Tan
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Correspondence to Jin-Tai Yu or Lan Tan.

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Lv, ZY., Tan, CC., Yu, JT. et al. Spreading of Pathology in Alzheimer’s Disease. Neurotox Res 32, 707–722 (2017). https://doi.org/10.1007/s12640-017-9765-2

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