Recent progress in the study of intracellular toxicity of amyloid β peptide in Alzheimer's disease

Amyloid beta (A beta) deposition is one of the major pathological markers of Alzheimer's disease (AD). Extracellular A beta toxicity has been studied for a long time in AD research field. However, controversial data show that extracellular A(3 load does not correlate with the dementia levels of AD patients and extracellular A(3 only induces significant cell death at non-physiological high concentrations. With the evolvement of A beta hypothesis, considerable attention has been devoted to the study of intracellular A beta toxicity recently. Intracellular A beta induces dramatic cell loss in AD transgenic models and in human primary neurons (at pM concentrations) through p53, Bax and caspase-6 pathways. Here, we review the generation, toxicity and possible pathways of intracellular A beta toxicity, and discuss the implication and current knowledge of intracellular A beta in neuronal cell loss in neurodegenerative diseases.