A novel PSENEN mutation in a patient with complaints of memory loss and a family history of dementia.
Presenilin enhancer-2 (PSENEN) is a fundamental component of the gamma-secretase protein complex involved in beta-amyloid precursor protein (beta APP) 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 A beta(1-40) and Abeta(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.
Albani
Diego
D
Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy. albani@marionegri.it
Batelli
Sara
S
Pesaresi
Marzia
M
Prato
Francesca
F
Polito
Letizia
L
Forloni
Gianluigi
G
Pantieri
Roberta
R