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Type II Diabetes Mellitus Accelerates Age-Dependent Aβ Pathology in Cynomolgus Monkey Brain

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Diabetes Mellitus

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1128))

Abstract

Accumulating evidence suggests that diabetes mellitus (DM) is one of the strongest risk factors for developing Alzheimer’s disease (AD). However, it remains unclear how DM accelerates AD pathology in the brain. Cynomolgus monkey (Macaca fascicularis) is one of the nonhuman primates used for biomedical research, and we can observe spontaneous formation of AD pathology, such as senile plaques (SPs) and neurofibrillary tangles (NFTs), with the advance of aging. Furthermore, obesity is occasionally observed and frequently leads to development of type II DM (T2DM) in laboratory-housed cynomolgus monkeys. These findings suggest that cynomolgus monkey is a useful species to study the relationship between T2DM and AD pathology. In T2DM-affected monkey brains, SPs were observed in frontal and temporal lobe cortices almost 5 years earlier than healthy control monkeys. Moreover, age-related endocytic pathology, such as intraneuronal accumulation of enlarged endosomes, was exacerbated in T2DM-affected monkey brains. Since accumulating evidences suggest that endocytic dysfunction is involved in Aβ pathology, T2DM may aggravate age-related endocytic dysfunction, leading to the acceleration of Aβ pathology.

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Acknowledgments

The author thanks Dr. Sachi Okabayashi, Dr. Nobuhiro Shimozawa, Dr. Yasuhiro Yasutomi, and Dr. Katsuhiko Yanagisawa for their great cooperation on T2DM-affected monkey brain analyses. The author also thanks Dr. Toshiki Uchihara for kindly providing the picture of tau pathology in cynomolgus monkey brains.

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  1. Section of Cell Biology and Pathology, Department of Alzheimer’s Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology (NCGG), Obu, Aichi, Japan

    Nobuyuki Kimura

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Correspondence to Nobuyuki Kimura .

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  1. Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

    Yusaku Nakabeppu

  2. Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Toshiharu Ninomiya

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Kimura, N. (2019). Type II Diabetes Mellitus Accelerates Age-Dependent Aβ Pathology in Cynomolgus Monkey Brain. In: Nakabeppu, Y., Ninomiya, T. (eds) Diabetes Mellitus. Advances in Experimental Medicine and Biology, vol 1128. Springer, Singapore. https://doi.org/10.1007/978-981-13-3540-2_7

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