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Beyond the pivotal role of A and tau, a spectrum of other factors may contribute to the pathology of AD, such as acetylcholine deficiency, neuroinflammation, oxidative stress, biometal dyshomeostasis, glutamate imbalance, insulin resistance, gut microbiome abnormalities, cholesterol homeostasis disruption, mitochondrial dysfunction, and autophagy abnormalities 29,30,31 (Fig

This suggests that mitochondrial activity influences ubiquitin-mediated proteasomal protein turnover, and hence amino acid availability in the cell, which may represent a feedback mechanism for both amino acid metabolism and mitochondrial homeostasis

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