Metabolic drivers of Alzheimer's disease pathogenesis: Impairments in glucose utilization, lipid homeostasis, and alternative substrate metabolism.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic concepts and pathways without primary empirical data or systematic review methodology.
PubMed 42442916 · doi:10.1016/bs.irn.2026.05.019
What was done
This is a narrative review synthesizing literature on the metabolic drivers of Alzheimer's disease (AD) pathogenesis. The authors examine mechanisms including mitochondrial dysfunction, glucose hypometabolism, impaired lipid homeostasis, ApoE4-mediated lipid trafficking failures, amino acid imbalances in the glutamate-glutamine cycle, the gut-brain axis, and the potential role of ketone bodies as an alternative energy substrate.
What was found
The abstract reports no quantitative data, effect sizes, or study counts. It qualitatively summarizes that AD involves loss of glucose transporters, downregulation of glycolytic enzymes, pathological lipid droplet accumulation, and systemic metabolic risk factors (such as type 2 diabetes and insulin resistance), while suggesting ketone bodies can partially bypass impaired glucose oxidation.
Why it matters
Framing metabolic failure and bioenergetic deficits as central upstream contributors to AD pathogenesis highlights opportunities for early metabolic biomarkers and therapeutic approaches targeting mitochondrial function, glucose restoration, and ketogenic support.
Limits
The abstract provides no primary data, sample sizes, search strategy, or quantitative findings. As a narrative overview, it does not evaluate study quality or resolve contradictory evidence across the primary literature.
Cited by
- supports In Alzheimer's disease, the brain's capacity to metabolize and utilize glucose declines.