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Interdisciplinary Program in Neuroscience

6월 4일 이종은 교수님 Abstract

관리자l2020-06-01l 조회수 128

Metabolic dysfunction and Alzheimer’s Disease


Jong Eun Lee

Department of Anatomy, BK21 Plus Project for Medical Science, Brain Research Institute, Yonsei University College of Medicine, Seoul, South Korea



The abnormal proteins deposits in the brain, including senile amyloid plaques(Aβ) and neurofibrillary tangles, has been recognized as the essential root of AD. However, recent imaging studies have shown that early, selective atrophy and glucose hypometabolism are detected in the medial temporal lobe of patient with early stage of AD, which suggests AD as a metabolic disease. Especially obesity and type 2 diabetes(T2D) are well known risk factors for Alzheimer’s disease(AD). MRI imaging shows that obese men have smaller brain volumes and increase the risk for AD. People who don’t engage in physical activity are at higher risk of developing cognitive decline over time. Also persons suffered with T2D are also at significantly increased risk for the development of Alzheimer’s disease due to brain insulin resistance. It is well established that reduced insulin signaling in neurons leads to neuronal dysfunction, accumulation of Aβ and phosphorylation of tau.

In this study, we try to define the correlation between metabolic dysfunction and AD pathophysiology and detect early metabolic changes in AD brains using by hyperpolarized 13C magnetic resonance spectroscopy, and define the metabolic changes in the brain of obese mice with AD pathology. We developed type 2 diabetes induced Alzheimer’s disease mouse model that exhibits obesity and insulin resistance, and obesity induced AD animal model. Male ICR mice were fed a 60% high fat diet (HFD) for 12 weeks and injected streptozotocin (STZ, 100mg/kg, i.p.) at 4th week for T2D-induced Alzheimer’s disease model, and mice were fed a 60% high fat diet (HFD) for 24 weeks for obesity induced AD model. Blood glucose level and weights of high fat diet group were significantly increased compared with normal diet group over a period of time. Insulin downstream signaling was blunted and the amount of Aβ42 and phosphorylated tau proteins was increased in brain of STZ-HFD group. In behavior test, STZ-HFD group and HFD group showed cognitive impairment.

Imaging study revealed both the amounts and speed of lactate conversion in the hippocampal areas were drastically increased in the HFD mouse brain. Change of adiponectin level in the brain was induced by HFD and this change might lead brain metabolism causing cognitive decline.


This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C2173)