β-amyloid Peptide Binds and Regulates Ectopic ATP Synthase α-Chain on Neural Surface

Accumulation of the amyloid beta protein (A beta) in the brain is an important step in the pathogenesis of Alzheimer's disease. Many molecules could bind with A beta, among which some molecules mediate A beta neuronal toxicity. Thus, it is of interest to study the binding proteins of A beta, and the functions that might be affected by A beta. In the present study, we observed that accumulation of alpha-subunit of ATP synthase is associated with aggregates of A beta proteins in amyloid plaques of amyloid precursor protein/presennillin-1 transgenic mice, and identified the alpha-subunit of ATP synthase as one of the A beta binding proteins on the plasma membrane of neural cells by Western blot and mass spectrometry. In order to evaluate the consequences of the interaction between A beta and surface alpha-subunit of ATP synthase, the extracellular ATP generation was analyzed, which showed that aggregated A beta partially inhibited the extracellular generation of ATP, but was unable to significantly induce a decrease in cell surface ATP synthase alpha on neurons. These results suggest that the cell surface ATP synthase alpha is a binding protein for A beta on neural cells, the functional inhibition of surface ATP synthase might be involved in machinery of brain malfunction in A beta-mediated pathogenesis of Alzheimer's disease.