Postmenopausal sarcopenia and Alzheimer’s disease: The interplay of mitochondria, insulin resistance, and myokines
Postmenopausal sarcopenia and Alzheimer’s disease (AD) are linked through a shared muscle–brain metabolic pathway. It highlights that women make up around two‑thirds of AD cases and that more than 60% are postmenopausal, then argues that loss of skeletal muscle mass and function in this group is closely associated with increased risk of cognitive decline.
Core pathophysiology
- Menopause‑related oestrogen decline and ageing drive skeletal muscle changes: mitochondrial dysfunction, increased reactive oxygen species, chronic low‑grade inflammation, and insulin resistance characterised by reduced GLUT4‑mediated glucose uptake into muscle fibres (shown in their mechanistic diagram).
- These changes accelerate muscle protein breakdown and fibre atrophy, leading to sarcopenia with reduced muscle mass, strength, and physical performance.
- Because contracting muscle is a major source of myokines, sarcopenia reduces secretion of BDNF, irisin and other myokines that normally support neuronal survival, synaptic plasticity, adult hippocampal neurogenesis, and learning/memory.
- In parallel, muscle mitochondrial dysfunction and insulin resistance feed back into systemic metabolic stress and inflammation, which aggravate brain mitochondrial dysfunction and neuronal insulin resistance, promoting amyloid‑β and tau pathology, synaptic loss, and cognitive decline characteristic of AD.
Integrated model
The authors propose a triangular interplay: menopause → oestrogen loss → muscle mitochondrial dysfunction, oxidative stress, GLUT4‑linked insulin resistance and sarcopenia → reduced myokines plus more systemic inflammation → impaired neurogenesis and synaptic function → higher risk and faster progression of AD in postmenopausal women. They position this muscle–brain axis as a key, potentially modifiable contributor to neurodegeneration and argue for interventions that target sarcopenia (muscle mass, mitochondrial health, insulin sensitivity, myokines) to slow cognitive deterioration in this population.
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