Amyloid-β(1-40) inhibits amyloid-β(1-42) induced activation of cytoplasmic phospholipase A2 and synapse degeneration

Journal of Alzheimer's Disease : JAD
Clive Bate, Alun Williams

Abstract

The pathogenesis of Alzheimer's disease (AD) is associated with the accumulation of amyloid-β (Aβ) peptides and the loss of synapses. The addition of Aβ(1-42) reduced the amount of synaptophysin in cultured cortical neurons in a model of AD-induced synapse degeneration. Aβ(1-42) also reduced the uptake of the fluorescent dye FM1-43 into synaptic recycling vesicles, a measure of synaptic function. We report that pre-mixing Aβ(1-40) with Aβ(1-42) significantly reduced the effects of Aβ(1-42) on synapses; it increased both synaptic vesicle recycling and synaptophysin content. These results are consistent with reports that Aβ(1-40) forms oligomers with Aβ(1-42) and that these are less toxic than Aβ(1-42) alone. In contrast, the addition of Aβ(1-40) did not affect the synapse degeneration induced by the prion-derived peptide PrP82-146. The addition of Aβ(1-40) reduced Aβ(1-42) induced activation of cytoplasmic phospholipase A2 (cPLA2) within synapses consistent with the hypothesis that Aβ(1-42) induced synapse degeneration is mediated by aberrant activation of synaptic cPLA2. Such observations raise the possibility that the amount of Aβ(1-40) produced within the brain is critical in determining the synapse damaging effects of Aβ(1-4...Continue Reading

Citations

Sep 9, 2011·The Journal of Biological Chemistry·Clive Bate, Alun Williams
Dec 9, 2010·Molecular Neurodegeneration·Clive BateAlun Williams
Jan 24, 2014·Molecular Neurobiology·Silvia BologninMario Buffelli
Apr 24, 2018·The Journal of Pharmacy and Pharmacology·Priya GhumatkarSadhana Sathaye
May 29, 2015·Journal of Peptide Science : an Official Publication of the European Peptide Society·Tian QiuYan-Mei Li

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