Intraneuronal Aβ accumulation and origin of plaques in Alzheimer's disease

Plaques are a defining neuropathological hallmark of Alzheimer's disease (AD) and the major constituent of plaques, the P-amyloid peptide (A beta), is considered to play an important role in the pathophysiology of AD. But the biological origin of A beta plaques and the mechanism whereby A beta is involved in pathogenesis have been unknown. A beta plaques were thought to form from the gradual accumulation and aggregation of secreted A beta in the extracellular space. More recently, the accumulation of A beta has been demonstrated to occur within neurons with AD pathogenesis. Moreover, intraneuronal A beta accumulation has been reported to be critical in the synaptic dysfunction, cognitive dysfunction and the formation of plaques in AD. Here we provide a historical overview on the origin of plaques and a discussion on potential biological and therapeutic implications of intraneuronal A beta accumulation for AD. (c) 2005 Published by Elsevier Inc.