Priority Research Papers:

Chronic diabetic states worsen Alzheimer neuropathology and cognitive deficits accompanying disruption of calcium signaling in leptin-deficient APP/PS1 mice

Shuai Zhang, Rui Chai, Ying-Ying Yang, Shi-Qi Guo, Shan Wang, Tian Guo, Shuang-Feng Xu, Yan-Hui Zhang, Zhan-You Wang and Chuang Guo _

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Oncotarget. 2017; 8:43617-43634. https://doi.org/10.18632/oncotarget.17116

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Shuai Zhang1, Rui Chai1, Ying-Ying Yang1, Shi-Qi Guo1, Shan Wang1, Tian Guo1, Shuang-Feng Xu1, Yan-Hui Zhang1, Zhan-You Wang1 and Chuang Guo1

1 College of Life and Health Sciences, Northeastern University, Shenyang, China

Correspondence to:

Chuang Guo, email:

Zhan-You Wang, email:

Keywords: Alzheimer’s disease, diabetes mellitus, β-amyloid, tau, calcium

Received: February 27, 2017 Accepted: April 03, 2017 Published: April 14, 2017


The coincidences between Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are so compelling that it is attractive to speculate that diabetic conditions might aggravate AD pathologies by calcium dysfunction, although the understanding of the molecular mechanisms involved remains elusive. The present work was undertaken to investigate whether calcium dyshomeostasis is associated with the exacerbated Alzheimer-like cognitive dysfunction observed in diabetic conditions in APP/PS1-ob/ob mice, which were generated by crossing ob/ob mice with APP/PS1 mice. We confirmed that the diabetic condition can aggravate not only Aβ deposition but also tau phosphorylation, synaptic loss, neuronal death, and inflammation, exacerbating cognitive impairment in AD mice. More importantly, we found that the diabetic condition dramatically elevated calcium levels in APP/PS1 mice, thereby stimulating the phosphorylation of the calcium-dependent kinases. Our findings suggest that controlling over-elevation of intracellular calcium may provide novel insights for approaching AD in diabetic patients and delaying AD progression.

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