Intracellular A beta and its Pathological Role in Alzheimer's Disease: Lessons from the Cellular to Animal Model

Accumulation of intraneuronal amyloid-beta peptide (A beta) appears to be an early event in Alzheimer's disease (AD), suggesting its important role in the neurodegenerative process of AD. It is indicated that intracellular A beta originates from a portion of A beta, which is not secreted and consequently remains intracellular, or alternatively from the secreted A beta, which is internalized into intracellular A beta pool. A number of cell and transgenic animal models are established to study the pathological role of intracellular A beta, and to screen for drugs against A beta aggregation and associated toxicity. A beta aggregates, particularly oligomers, may lead to synaptic dysfunction and neuronal loss. Screened from high-throughput methods, a number of cell-permeable agents reduce the aggregation of intracellular A beta and antagonize its cytotoxicity by inhibiting the formation of A beta oligomers in vivo. The multi-functional roles of A beta in alternate pathways and associated clinical implications for AD treatment are also discussed.