New light on gamma secretase failures in AD

In a study published in Cell Reports this week, researchers from Osaka University added another possible explanation for why gamma secretase/presenilin inhibitors have failed in Alzheimer’s disease trials.

The gamma secretase complex acts downstream of beta-site APP-cleaving enzyme (BACE) in the processing of amyloid precursor protein (APP) to generate beta amyloid, a toxic peptide that forms extracellular aggregates in the brains of AD patients. Several inhibitors of the complex or its catalytic subunit presenilin 1 (PSEN1; PS1) have been tested in AD trials, but none have succeeded...