A novel PSENEN mutation in a patient with complaints of memory loss and a family history of dementia

Abstract Presenilin enhancer-2 (PSENEN) is a fundamental component of the γ-secretase protein complex involved in β-amyloid precursor protein (βAPP) processing, a key event in Alzheimer’s disease (AD) etiopathogenesis. In a mild cognitive impairment (MCI)-diagnosed woman, belonging to a family with a positive history for AD, we found that a novel PSENEN mutation (S73F) was the only genetic alteration of relevance. The mutation was absent in 253 age-matched controls. In an attempt to learn the biochemical effects of this mutation, we cultured skin primary fibroblasts from the patient and her daughter, and we assessed Aβ(1–40) and Aβ(1–42) production. We did not find any relevant differences in comparison to age-matched, normal subjects. Although our data do not definitively support a pathogenetic role for this mutation, it does not appear to be a common polymorphism. Further follow-up is warranted in this family.