Mitochondrial Bioenergetics and Metabolic Hormones in Alzheimer’s Disease and Related Dementias

Alzheimer’s disease is increasingly viewed as a disorder of brain energy metabolism with a hallmark protein aggregation. Reduced cerebral glucose use appears years before symptoms, and mitochondrial impairment is among the earliest changes in vulnerable neurons. Defects in oxidative phosphorylation, mitochondrial dynamics, calcium handling and reactive oxygen species production compromise synaptic function and neuronal survival and may promote amyloid and tau pathology. Mitochondrial function is closely regulated by metabolic hormones. Insulin, thyroid hormones, glucocorticoids, leptin, adiponectin and incretins such as GLP-1 all influence mitochondrial biogenesis, substrate use and energy output, often through shared pathways such as PGC-1α, AMPK and mTOR. Changes in these hormones with age, and in conditions such as type 2 diabetes, obesity and chronic stress, may therefore weaken neuronal bioenergetics and raise Alzheimer’s risk. Despite growing evidence, mitochondrial biology and hormonal signalling are usually studied separately. A clearer view of how they interact could explain why metabolic disease increases risk of cognitive impairment and AD and point to new treatment strategies.This Research Topic aims to establish how mitochondrial impairment and metabolic hormone signalling are interconnected in Alzheimer’s disease, and how this metabolic paradigm can inform better treatment. We seek mechanistic studies showing how hormones such as insulin, thyroid hormones, glucocorticoids, leptin, adiponectin and incretins regulate mitochondrial biogenesis, dynamics, bioenergetics and quality control in neurons and glia, and how this regulation fails with ageing and disease. We particularly welcome work on the shared signalling hubs, including PGC-1α, AMPK, mTOR and sirtuins, that link hormonal and mitochondrial dysfunction, and on how metabolic disorders such as type 2 diabetes and obesity worsen brain bioenergetics. We also invite studies proposing adjustments to current therapeutic strategies in light of this framework. Examples include repurposing metabolic drugs such as GLP-1 receptor agonists and metformin, ketone-based and dietary interventions, NAD+ precursors and mitochondria-targeted compounds. Studies combining experimental models with human biomarkers, imaging or clinical data are strongly encouraged. Together, these contributions will clarify how metabolic and mitochondrial failure drive Alzheimer’s disease and how targeting them could change disease course.We welcome submissions addressing, but not limited to, the following themes:• Mitochondrial bioenergetics, dynamics and quality control in Alzheimer’s disease• Regulation of neuronal and glial mitochondria by insulin, thyroid hormones, glucocorticoids, leptin, adiponectin and incretins• Shared signaling hubs (PGC-1α, AMPK, mTOR, sirtuins) linking hormonal and mitochondrial dysfunction• Type 2 diabetes, obesity and chronic stress as drivers of impaired brain bioenergetics• Cerebral glucose hypometabolism and alternative energy substrates• Interactions between metabolic failure and amyloid and tau pathology• Metabolic and mitochondrial biomarkers, including imaging, for early detection and monitoring• Repurposed metabolic drugs, ketone-based, dietary and NAD± based interventions• Mitochondria-targeted therapies and combination strategiesWe encourage a wide range of submissions, including original research, methods papers, brief research reports, data reports, systematic reviews, mini reviews and perspectives. Topic editors: Ashu Johri, Masashi Tanaka Source: https://www.frontiersin.org/research-topics/87420/mitochondrial-bioenergetics-and-metabolic-hormones-in-alzheimers-disease-and-related-dementias