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The Role of PICALM in Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is a highly heritable disease (with heritability up to 76 %) with a complex genetic profile of susceptibility, among which large genome-wide association studies (GWASs) pointed to the phosphatidylinositol-binding clathrin assembly protein (PICALM) gene as a susceptibility locus for late-onset Alzheimer’s disease (LOAD) incidence. Here, we summarize the known functions of PICALM and discuss its genetic polymorphisms and their potential physiological effects associated with LOAD. Compelling data indicated that PICALM affects AD risk primarily by modulating production, transportation, and clearance of β-amyloid (Aβ) peptide, but other Aβ-independent pathways are discussed, including tauopathy, synaptic dysfunction, disorganized lipid metabolism, immune disorder, and disrupted iron homeostasis. Finally, given the potential involvement of PICALM in facilitating AD occurrence in multiple ways, it might be possible that targeting PICALM might provide promising and novel avenues for AD therapy.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (81000544, 81171209, and 81371406) and Shandong Provincial Natural Science Foundation, China (ZR2010HQ004 and ZR2011HZ001).

Conflict of Interest

The authors declare no conflicts of interest.

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Authors and Affiliations

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

    Wei Xu, Lan Tan & Jin-Tai Yu

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  1. Wei Xu
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  2. Lan Tan
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Correspondence to Lan Tan or Jin-Tai Yu.

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Xu, W., Tan, L. & Yu, JT. The Role of PICALM in Alzheimer’s Disease. Mol Neurobiol 52, 399–413 (2015). https://doi.org/10.1007/s12035-014-8878-3

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  • DOI: https://doi.org/10.1007/s12035-014-8878-3

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