Assessing Neuroprotective Agents for Aß-Induced Neurotoxicity.

Alzheimer's disease (AD) is a relentlessly progressive neurodegenerative disease, currently incurable, which presents one of the largest unmet needs in medicine. AD is histologically characterized by the accumulation of extracellular amyloid-beta (Aß), evident as senile plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. However, the levels of diffusible extracellular Aß, a neuropeptide largely present in oligomeric form, rise by orders of magnitude many years before evident pathology and subsequent AD diagnosis. The long delay in neurotoxicity and synaptic dysfunction triggered by Aß and driven by abnormal tau indicates the presence of inherent neuroprotective systems in brain. Here, we propose that strategic approaches for the identification and implementation of neuroprotective agents could provide novel therapeutics for this devastating disease.