Oligomeric Aβ-induced synaptic dysfunction in Alzheimer’s disease

Alzheimer's disease (AD) is a devastating disease characterized by synaptic and neuronal loss in the elderly. Compelling evidence suggests that soluble amyloid-β peptide (Aβ) oligomers induce synaptic loss in AD. Aβ-induced synaptic dysfunction is dependent on overstimulation of N-methyl-D-aspartate receptors (NMDARs) resulting in aberrant activation of redox-mediated events as well as elevation of cytoplasmic Ca2+, which in turn triggers downstream pathways involving phospho-tau (p-tau), caspases, Cdk5/dynamin-related protein 1 (Drp1), calcineurin/PP2B, PP2A, Gsk-3β, Fyn, cofilin, and CaMKII and causes endocytosis of AMPA receptors (AMPARs) as well as NMDARs. Dysfunction in these pathways leads to…

• UD
  U.S. Department of Defense

  Awards: W81XWH-13-0053, W81XWH, W81XWH-13
• AA
  Alzheimer's Association
• NI
  National Institutes of Health

  Awards: NS086890, P01 HD29587, R01AG038710, R01AG044420, W81XWH, R21 NS080799, R01NS046673, R01 NS086890, R01AG021173
• UO
  University of California, San Diego