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Abstract
Synaptic dysfunction is the earliest and most critical pathological feature of Alzheimer's disease (AD).
- Cognitive decline in AD is directly linked to synaptic dysfunction.
- Impairments in Aβ aggregation, tau pathology, calcium imbalance, oxidative stress, and neuroinflammation disrupt dendritic spine morphology and synaptic connectivity.
- Neurotrophins like brain-derived neurotrophic factor and TrkB signaling, along with hormonal influences and lipid regulators, are involved in modulating synaptic resilience.
- Pharmacological agents, including cholinesterase inhibitors and NMDA receptor modulators, as well as nutraceuticals like resveratrol and omega-3 fatty acids, may have therapeutic potential.
- Emerging technologies such as iPSC-derived neuronal models and advanced neuroimaging biomarkers could help in monitoring synaptic integrity.
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