Intraneuronal Abeta 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 beta-amyloid peptide (Abeta), is considered to play an important role in the pathophysiology of AD. But the biological origin of Abeta plaques and the mechanism whereby Abeta is involved in pathogenesis have been unknown. Abeta plaques were thought to form from the gradual accumulation and aggregation of secreted Abeta in the extracellular space. More recently, the accumulation of Abeta has been demonstrated to occur within neurons with AD pathogenesis. Moreover, intraneuronal Abeta 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 Abeta accumulation for AD.
Gouras
Gunnar K
GK
Laboratory of Alzheimer's disease Neurobiology, Department of Neurology & Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA. gkgouras@med.cornell.edu
Almeida
Claudia G
CG
Takahashi
Reisuke H
RH
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008954:Models, Biological; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D058225:Plaque, Amyloid / Q000378:metabolism*
D016229:Amyloid beta-Peptides