Relative amounts of amyloid-β peptides of different lengths are altered in the brains of Alzheimer’s disease patients. In this report, Dolev and colleagues show that neuronal activity patterns differentially regulate the production of amyloid-β isoforms by modifying the molecular conformation of presenilin-1, the catalytic subunit of γ-secretase that cleaves amyloid precursor protein to release amyloid-β. The amyloid-β40/42 ratio has been suggested to be critical for Alzheimer’s disease pathogenesis. These results therefore have importance for specific aspects of Alzheimer disease initiation and progression.
Dolev I, Fogel H, Milshtein H, Berdichevsky Y, Lipstein N, Brose N, Gazit N, Slutsky I: Spike bursts increase amyloid-β 40/42 ratio by inducing a presenilin-1 conformational change. Nature Neuroscience [ Epub ahead of print, April 7, 2013; doi:10.1038/nn.3376 ].