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The metabolic hypothesis of Alzheimer’s disease

John Didsbury, PhD, T3D Therapeutics, Inc., Research Triangle Park, NC, talks on Alzheimer’s disease as a neuro-metabolic disease. Dysregulated glucose and lipid metabolism are key features of Alzheimer’s disease, with changes shown to precede classical clinical symptoms by many years. The metabolic hypothesis of disease states that impaired glucose metabolism due to insulin resistance starts a chain of events, fueling a positive feedback loop of metabolic, structural, and stress changes. This metabolic dysfunction is thought to lead to impaired energy production and altered protein post-translational modification, causing misfolding and thus, the defining pathological plaques and tangles seen in Alzheimer’s. These pathologies in turn perpetuate glucose energy and lipid metabolism dysfunctions. Since metabolism alterations precede structural change in Alzheimer’s disease, ameliorating this dysfunction may effectively break the neurodegenerative cycle. This interview took place at the Alzheimer's Association International Conference (AAIC) 2022 in San Diego, CA.