The neuromodulatory fragility hypothesis of Alzheimer's disease pathogenesis - PubMed
2 days ago
- #Alzheimer's disease
- #neuromodulation
- #pathogenesis
- The neuromodulatory fragility hypothesis proposes that diverse risk factors for Alzheimer's disease (AD) converge on fragile neuromodulatory subcortical systems.
- Neuromodulatory projection neurons are uniquely fragile due to their large size, sparse myelination, and high metabolic demands.
- The increased prevalence of AD in older adults reflects a universal weakness in these systems, exacerbated by aging-related deterioration.
- Dysfunction in neuromodulatory systems can explain both tau hyperphosphorylation and amyloid beta plaque formation, the two hallmarks of AD.
- Strengthening or preserving these systems in midlife is suggested as the most effective strategy for preventing AD.