Amyloid-[beta]-induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks

摘要: Alzheimer's disease is the most frequent neurodegenerative disorder and common cause of dementia in elderly. Diverse lines evidence suggest that amyloid-beta (Abeta) peptides have a causal role its pathogenesis, but underlying mechanisms remain uncertain. Here we discuss recent Abeta may be part mechanism controlling synaptic activity, acting as positive regulator presynaptically negative postsynaptically. The pathological accumulation oligomeric assemblies depresses excitatory transmission at level, also triggers aberrant patterns neuronal circuit activity epileptiform discharges network level. Abeta-induced dysfunction inhibitory interneurons likely increases synchrony among principal cells contributes to destabilization networks. Strategies block these effects prevent cognitive decline disease. Potential obstacles next steps toward this goal are discussed.