Improper processing of amyloid precursor protein (APP) in the brain gives rise to β-amyloid plaques, a hallmark of Alzheimer’s disease (AD). Familial forms of AD often arise from changes in proteins that regulate APP processing, such as γ-secretase, which cleaves APP and other type I transmembrane proteins. McMains et al. identify γ-secretase in Dictyostelium that – although highly diverged from human γ-secretase – precisely cleaves human APP. So, Dictyostelium, a primitive eukaryote that is easy to study, might be a useful model to understand γ-secretase function in the context of familial mutations associated with AD.

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