APP and early-onset autosomal dominant Alzheimer disease: γ-Secretase is a key player in the pathology of Alzheimer disease (AD) as it catalyzes the final step in the processing of the amyloid precursor protein (APP) leading to the formation of the neurotoxic amyloid β-peptide (Aβ), which is the major constituent of the amyloid plaques in the brains of AD patients [1].