Navigation
Interactions between menopause and high-fat diet on cognition and pathology in a mouse model of Alzheimer’s disease
Introduction: Approximately two-thirds of individuals diagnosed with Alzheimer’s disease (AD) are post-menopausal women. Menopause is known to elevate the risk of dementia, partly due to its association with an increased likelihood of developing metabolic disorders, a recognized risk factor for cognitive decline. This study explored how menopause and a high-fat (HF) diet influence cognitive and pathological outcomes in a mouse model of AD. Methods: Female AppNL-F mice, at 3 months of age, were administered either 4-vinylcyclohexene diepoxide (to simulate menopause) or a vehicle solution. They were then maintained on either a standard diet (10% fat) or an HF diet (60% fat) until they reached 10 months. Results: A combined effect of menopause and HF diet led to impaired recognition memory. Menopause alone did not affect the accumulation of amyloid plaques. However, it did alter microglial activity, reduce myelin in the corpus callosum, and impact neurogenesis in the hippocampus, with some of these effects being influenced by dietary fat intake. Discussion: These findings underscore the importance of incorporating endocrine aging into AD animal models and provide insight into how hormonal and metabolic changes may interact in the development of Alzheimer’s pathology.
[NPID: Alzheimer’s disease; amyloid; menopause; metabolic disease; microglia; neurogenesis; white matter].
Year: 2025
