Volume 8 Supplement 1

Molecular Neurodegeneration: Basic biology and disease pathways

Open Access

Abeta is prerequisite, but insufficient to cause tau phosphorylation in vivo: tau phosphorylation in APP mice by diabetes

  • Naoyuki Sato1
Molecular Neurodegeneration20138(Suppl 1):P35

https://doi.org/10.1186/1750-1326-8-S1-P35

Published: 13 September 2013

Background

Epidemiological studies suggest that diabetes mellitus increases the risk of onset of Alzheimer disease (AD). However, the underlying mechanisms have not been fully understood. Retrospective studies indicate that diabetes does not increase senile plaques. On the other hand, a Japanese cohort, Hisayama study suggested that insulin resistance in midlife increased the risk of development of senile plaques. Therefore, the aim of this study is to understand the mechanisms by which diabetes increase the risk of AD by dividing them into two phases; 1) before and 2) after the development of senile plaques.

Methods

1) To test whether insulin resistance increases Abeta accumulation in the brain, we fed wild-type mice with a high-fat diet and measured the levels of Abeta in the brain. 2) To investigate the effects of diabetes on AD, we further analyzed the phenotypes of APP+ob/ob mice [1], which showed the increased cerebral amyloid angiopathy and impaired insulin signaling, especially focusing on tau phosphorylation.

Results

1) Six months on a high fat diet increased Abeta40 in B6C mice brain. 2) 18 month old APP+ob/ob mice showed highly increased level of tau phosphorylation in the brain. Furthermore, a high fat diet increased plasma Abeta levels in APP/PS1 mice, but not in wild type mice.

Conclusion

Tau phosphorylation is increased by diabetes in APP mice, suggesting that Abeta is prerequisite, but insufficient to cause tau phosphorylation in vivo. Abeta accumulation, insulin signaling and tau phosphorylation might play essential roles in the pathological interaction between AD and diabetes [2]. Of note, a vicious cycle likely underlies the interaction between AD and diabetes. High fat diet-induced elevation of plasma Abeta level might be involved in this mutual pathological interaction between the diseases [3, 4]. These results suggest that diabetes disrupts homeostasis against AD.

Authors’ Affiliations

(1)
Department of Clinical Gene Therapy, Department of Geriatric Medicine

References

  1. Shuko Takeda, Naoyuki Sato, et al: Diabetes accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes. Proc Natl Acad Sci U S A. 2010, 107: 7036-7041. 10.1073/pnas.1000645107.View ArticleGoogle Scholar
  2. Naoyuki Sato, et al: Role of insulin signaling in the interaction between Alzheimer disease and diabetes mellitus: a missing link to therapeutic potential. Current Aging Science. 2011, 4: 118-127. 10.2174/1874609811104020118.View ArticleGoogle Scholar
  3. Shuko Takeda, Naoyuki Sato, et al: Oral Glucose Loading Modulates Plasma Abeta Level in Alzheimer Disease Patients: Potential Diagnostic Method for Alzheimer Disease. Dementia and Geriatric Cognitive Disorders. 2012, 34: 25-30. 10.1159/000338704.View ArticleGoogle Scholar
  4. Naoyuki Sato, et al: Plasma Abeta: A Possible Missing Link Between Alzheimer Disease and Diabetes. Diabetes. 2013, 62: 1005-1006. 10.2337/db12-1549.View ArticleGoogle Scholar

Copyright

© Sato; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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