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Membrane Aging as the Real Culprit of Alzheimer’s Disease: Modification of a Hypothesis

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Abstract

Our previous studies proposed that Alzheimer’s disease (AD) is a metabolic disorder and hypothesized that abnormal brain glucose metabolism inducing multiple pathophysiological cascades contributes to AD pathogenesis. Aging is one of the great significant risk factors for AD. Membrane aging is first prone to affect the function and structure of the brain by impairing glucose metabolism. We presume that risk factors of AD, including genetic factors (e.g., the apolipoprotein E ε4 allele and genetic mutations) and non-genetic factors (such as fat, diabetes, and cardiac failure) accelerate biomembrane aging and lead to the onset and development of the disease. In this review, we further modify our previous hypothesis to demonstrate “membrane aging” as an initial pathogenic factor that results in functional and structural alterations of membranes and, consequently, glucose hypometabolism and multiple pathophysiological cascades.

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Acknowledgements

This review was supported by the ‘‘973’’ project (2011CBA00400), the National Natural Science Foundation of China (81071019), the Fund for Outstanding Academic Leaders in Shanghai (11XD1401500), and the fund for Medical Emerging Cutting-edge Technology in Shanghai (SHDC12012114).

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  1. Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Qiujian Yu & Chunjiu Zhong

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Yu, Q., Zhong, C. Membrane Aging as the Real Culprit of Alzheimer’s Disease: Modification of a Hypothesis. Neurosci. Bull. 34, 369–381 (2018). https://doi.org/10.1007/s12264-017-0192-4

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