김범수 (University of Michigan)

한빛사논문

조회250

김범수Bhumsoo Kim

University of Michigan

J. Extracell. Vesicles, Nov 2023, 12 (11) 12340 | https://doi.org/10.1002/jev2.12340 Palmitate and glucose increase amyloid precursor protein in extracellular vesicles: Missing link between metabolic syndrome and Alzheimer's disease

Bhumsoo Kim ^1,2, Yoon-Tae Kang ³, Faye E Mendelson^1,2, John M Hayes^1,2, Masha G Savelieff², Sunitha Nagrath ³, Eva L Feldman ^1,2

¹Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.

²NeuroNetwork for Emerging Therapies, University of Michigan, Ann Arbor, Michigan, USA.

³Department of Chemical Engineering and Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan, USA.

CORRESPONDING AUTHOR : Eva L. Feldman

Abstract

The metabolic syndrome (MetS) and Alzheimer's disease share several pathological features, including insulin resistance, abnormal protein processing, mitochondrial dysfunction and elevated inflammation and oxidative stress. The MetS constitutes elevated fasting glucose, obesity, dyslipidaemia and hypertension and increases the risk of developing Alzheimer's disease, but the precise mechanism remains elusive. Insulin resistance, which develops from a diet rich in sugars and saturated fatty acids, such as palmitate, is shared by the MetS and Alzheimer's disease. Extracellular vesicles (EVs) are also a point of convergence, with altered dynamics in both the MetS and Alzheimer's disease. However, the role of palmitate- and glucose-induced insulin resistance in the brain and its potential link through EVs to Alzheimer's disease is unknown. We demonstrate that palmitate and high glucose induce insulin resistance and amyloid precursor protein phosphorylation in primary rat embryonic cortical neurons and human cortical stem cells. Palmitate also triggers insulin resistance in oligodendrocytes, the supportive glia of the brain. Palmitate and glucose enhance amyloid precursor protein secretion from cortical neurons via EVs, which induce tau phosphorylation when added to naïve neurons. Additionally, EVs from palmitate-treated oligodendrocytes enhance insulin resistance in recipient neurons. Overall, our findings suggest a novel theory underlying the increased risk of Alzheimer's disease in MetS mediated by EVs, which spread Alzheimer's pathology and insulin resistance.

논문정보

형식Research article
게재일2023년 11월 (BRIC 등록일 2023-11-02)
연구진국외 연구진
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