Nutritional Deficiency in Early Life Facilitates Aging-Associated Cognitive Decline

Kang, Yu Ri; Zhang, Yun; Feng, Zijuan; Liu, Mingjing; Li, Yanhua; Yang, Huan; Wang, Dan; Zheng, Ling‐Ling; Lou, Dandan; Li, Cheng; Chen, Chunjiang; Zhou, Weitao; Feng, Yi; Li, Xiaoyong; Duan, Jianzhong; Yu, Mengjiao; Yang, Shou; Liu, Yuhang; Wang, Xin; Deng, Bo; Liu, Chenghui; Yao, Xiu-Qing; Zhu, Chi; Liang, Chun-Rong; Zeng, Xiaolong; Ren, Sisi; Li, Qunying; Zhong, Yin; Zhang, Yong; Kang, Junren; Yan, Yong; Meng, Huaqing; Zhong, Zhaohui; Zhou, Weihui; Wang, Yanjiang; Li, Tingyu; Song, Weihong

doi:10.2174/1567205014666170425112331

Cited by 41 publications

(25 citation statements)

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“…Cognitive decline is one of the major consequences of diabetes, and growing evidence supports a strong link between AD-related dementia and diabetes (24,(34)(35)(36)(37). The prevalence of mild cognitive impairments is dramatically increased in individuals with diabetes (38,39), and diabetes also significantly accelerates the progression from mild cognitive impairments to dementia (40). Consistent with these studies, our clinical survey revealed that individuals experiencing T2DM had markedly lower MMSE scores compared with nondiabetic healthy control subjects.…”

Section: Discussionsupporting

confidence: 84%

Formaldehyde induces diabetes‐associated cognitive impairments

et al. 2018

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Patients with type 2 diabetes mellitus (T2DM) often develop cognitive impairments and have an increased risk of developing Alzheimer's disease. Hyperglycemia is a major characteristic of T2DM, but how elevated glucose levels lead to cognitive decline remains elusive. Here, we report that patients with T2DM and mutations in the formaldehyde (FA)-degrading enzyme aldehyde dehydrogenase 2 ( ALDH2) gene had higher levels of FA and more severe dementia. Injection of FA induced hyperglycemia and cognitive deficits in rats. Ablation of gene expression of ALDH2, the main enzyme to oxidize FA, resulted in abnormally high levels of hippocampal FA, leading to hyperglycemia and cognitive impairments as well as potentiating streptozotocin-induced diabetes development in ALDH2 knockout mice. We found that FA interacts with insulin to form FA-insulin adducts, and these FA-insulin adducts caused insulin deficiency, contributing to memory decline in diabetic rodent models. Reduction of FA by transgenic overexpression of human ALDH2 attenuates hyperglycemia and alleviates cognitive deficits in diabetic mouse models. These findings suggest that excess FA plays a critical role in mediating diabetes-related dementia. Targeting FA and its metabolizing enzyme ALDH2 may be a valid approach for preventing and treating dementia in diabetes mellitus.-Tan, T., Zhang, Y., Luo, W., Lv, J., Han, C., Hamlin, J. N. R., Luo, H., Li, H., Wan, Y., Yang, X., Song, W., Tong, Z. Formaldehyde induces diabetes-associated cognitive impairments.

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Section: Discussionsupporting

confidence: 84%

Formaldehyde induces diabetes‐associated cognitive impairments

et al. 2018

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“…Alzheimer's disease (AD) is the most common neurodegenerative disease leading to dementia (1). Deposition of amyloid β protein (Aβ) to form neuritic plaques in the brain is a hallmark of AD neuropathology (2).…”

Section: Introductionmentioning

confidence: 99%

BACE2, a conditional β-secretase, contributes to Alzheimer’s disease pathogenesis

Wang

Cai

et al. 2019

JCI Insight

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“…The etiology of LOAD is not yet fully understood. A combination of multiple factors is believed to contribute to the pathogenesis of LOAD, including aging, genetics, nutrition, lifestyle and chronic metabolic disorders (ADI; Qiu et al, 2009 ; Yang and Song, 2013 ; Kang et al, 2017 ; Zeng et al, 2017 ; Zhang and Song, 2017 ). Among them, aging has been demonstrated as the greatest risk factor of AD.…”

Section: Introductionmentioning

confidence: 99%

Modifications and Trafficking of APP in the Pathogenesis of Alzheimer’s Disease

Wang

Zhou

et al. 2017

Front. Mol. Neurosci.

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Alzheimer’s disease (AD), the most common neurodegenerative disorder, is the leading cause of dementia. Neuritic plaque, one of the major characteristics of AD neuropathology, mainly consists of amyloid β (Aβ) protein. Aβ is derived from amyloid precursor protein (APP) by sequential cleavages of β- and γ-secretase. Although APP upregulation can promote AD pathogenesis by facilitating Aβ production, growing evidence indicates that aberrant post-translational modifications and trafficking of APP play a pivotal role in AD pathogenesis by dysregulating APP processing and Aβ generation. In this report, we reviewed the current knowledge of APP modifications and trafficking as well as their role in APP processing. More importantly, we discussed the effect of aberrant APP modifications and trafficking on Aβ generation and the underlying mechanisms, which may provide novel strategies for drug development in AD.

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Nutritional Deficiency in Early Life Facilitates Aging-Associated Cognitive Decline

Abstract: These findings demonstrate that exposure to famine during early life including prenatal period and early childhood facilitates aging-associated cognitive deficits.

Cited by 41 publications

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Formaldehyde induces diabetes‐associated cognitive impairments

Formaldehyde induces diabetes‐associated cognitive impairments

BACE2, a conditional β-secretase, contributes to Alzheimer’s disease pathogenesis

Modifications and Trafficking of APP in the Pathogenesis of Alzheimer’s Disease

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