Intraneuronal beta-amyloid accumulation and synapse pathology in Alzheimer's disease.
The aberrant accumulation of aggregated beta-amyloid peptides (Abeta) as plaques is a hallmark of Alzheimer's disease (AD) neuropathology and reduction of Abeta has become a leading direction of emerging experimental therapies for the disease. The mechanism(s) whereby Abeta is involved in the pathophysiology of the disease remain(s) poorly understood. Initially fibrils, and subsequently oligomers of extracellular Abeta have been viewed as the most important pathogenic form of Abeta in AD. More recently, the intraneuronal accumulation of Abeta has been described in the brain, although technical considerations and its relevance in AD have made this a controversial topic. Here, we review the emerging evidence linking intraneuronal Abeta accumulation to the development of synaptic pathology and plaques in AD, and discuss the implications of intraneuronal beta-amyloid for AD pathology, biology, diagnosis and therapy.
Gouras
Gunnar K
GK
Department for Neurology and Neuroscience, Weill Cornell Medical College, New York, NY 10065, USA. gkgouras@med.cornell.edu
Tampellini
Davide
D
Takahashi
Reisuke H
RH
Capetillo-Zarate
Estibaliz
E
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D013569:Synapses / Q000378:metabolism / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016875:tau Proteins