Modulation of Brain Hyperexcitability: Potential New Therapeutic Approaches in Alzheimer's Disease.

摘要: People with Alzheimer's disease (AD) have significantly higher rates of subclinical and overt epileptiform activity. In animal models, oligomeric Aβ amyloid is able to induce neuronal hyperexcitability even in the early phases disease. Such aberrant activity subsequently leads downstream accumulation toxic proteins, ultimately further neurodegeneration silencing mediated by concomitant tau accumulation. Several neurotransmitters participate initial hyperexcitable state, increased synaptic glutamatergic tone decreased GABAergic inhibition. These changes appear activate excitotoxic pathways and, ultimately, cause reduced long-term potentiation, depression, inhibitory remodelling at network level. Brain has therefore been identified as a potential target for therapeutic interventions aimed enhancing cognition, possibly, modification longer term. Clinical trials are ongoing evaluate efficacy targeting AD, levetiracetam showing some encouraging effects. Newer compounds techniques, such gene editing via viral vectors or brain stimulation, also show promise. Diagnostic challenges include identifying best biomarkers measuring sub-clinical discharges. Determining timing any intervention critical future will need carefully stratify participants respect phase pathology.