title: Synaptic mitochondrial pathology in Alzheimer's disease.
abstract: CONCLUSIONS
  Synaptic degeneration, an early pathological feature in Alzheimer's disease (AD), is closely correlated to impaired cognitive function and memory loss. Recent studies suggest that involvement of amyloid-beta peptide (Aβ) in synaptic mitochondrial alteration underlies these synaptic lesions. Thus, to understand the Aβ-associated synaptic mitochondrial perturbations would fortify our understanding of synaptic stress in the pathogenesis of AD.
  
  
  BACKGROUND
  Increasing evidence suggests that synaptic mitochondrial dysfunction is strongly associated with synaptic failure in many neurodegenerative diseases including AD. Based on recent findings in human AD subjects, AD animal models, and AD cellular models, synaptic mitochondria undergo multiple malfunctions including Aβ accumulation, increased oxidative stress, decreased respiration, and compromised calcium handling capacity, all of which occur earlier than changes seen in nonsynaptic mitochondria before predominant AD pathology. Of note, the impact of Aβ on mitochondrial motility and dynamics exacerbates synaptic mitochondrial alterations.
  
  
  RESULTS
  Synaptic mitochondria demonstrate early deficits in AD; in combination with the role that synaptic mitochondria play in sustaining synaptic functions, deficits in synaptic mitochondria may be a key factor involved in an early synaptic pathology in AD.
  
  
  CONCLUSIONS
  The importance of synaptic mitochondria in supporting synapses and the high vulnerability of synaptic mitochondria to Aβ make them a promising target of new therapeutic strategy for AD.
authors.affiliation: Higuchi Bioscience Center, University of Kansas, Lawrence, Kansas, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Du
authors.forename: Lan
authors.initials: L
authors.lastname: Guo
authors.forename: Shirley ShiDu
authors.initials: SS
authors.lastname: Yan
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D013569:Synapses / Q000378:metabolism*