The recently discovered interaction between Presenilin 1 (PS1), a catalytic subunit of γ-secretase responsible for generating amyloid-β peptides, and GLT-1, a major glutamate transporter in the brain (EAAT2), provides a mechanistic link between these two key factors involved in Alzheimer’s disease (AD) pathology. Here, PSEN1 is linked to early-onset autosomal dominant Alzheimer disease.