Abstract
β-Amyloid peptide accumulation plays a central role in the pathogenesis of Alzheimer's disease. Aberrant β-amyloid buildup in the brain has been shown to be present both in the extracellular space and within neurons. Synapses are important targets of β-amyloid, and alterations in synapses better correlate with cognitive impairment than amyloid plaques or neurofibrillary tangles. The link between β-amyloid and synapses became even tighter when it was discovered that β-amyloid accumulates within synapses and that synaptic activity modulates β-amyloid secretion. Currently, a central question in Alzheimer's disease research is what role synaptic activity plays in the disease process, and how specifically β-amyloid is involved in the synaptic dysfunction that characterizes the disease.
Highlights
Reviewed by: Peizhong Mao, Oregon Health and Science University, USA Qitao Ran, University of Texas, USA; University of Texas Health Science Center at San Antonio, USA P
Synapses are considered the earliest site of pathology, and synaptic loss is the best pathological correlate of cognitive impairment in Alzheimer’s disease (AD) (Hamos et al, 1989; DeKosky and Scheff, 1990; Terry et al, 1991; Selkoe, 2002; Coleman and Yao, 2003)
The first direct association between Aβ peptide and synapse pathologies in the brain was provided by immunoelectron microscopy (IEM); this showed that aberrant Aβ42 accumulation within distal neurites and synapses was directly associated with pathology (Takahashi et al, 2002)
Summary
Reviewed by: Peizhong Mao, Oregon Health and Science University, USA Qitao Ran, University of Texas, USA; University of Texas Health Science Center at San Antonio, USA P. Increased secretion of Aβ induced by synaptic activity could lead to damage and loss of synapses and to progressive accumulation of extracellular Aβ into amyloid plaques, which are important hallmarks of AD. Recent cell biological studies provided evidence that synaptic activation reduces levels of intraneuronal Aβ and protects synapses in models of AD, despite a concomitant increase in Aβ secretion (Tampellini et al, 2009).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
