Presenilin-1 mutation E318G and familial Alzheimer's disease in the Italian population

Diego Albani, Ignazio Roiter, Vladimiro Artuso, Sara Batelli, Francesca Prato, Marzia Pesaresi, Daniela Galimberti, Elio Scarpini, Amalia Bruni, Massimo Franceschi, Maria Rita Piras, Annamaria Confaloni, Gianluigi Forloni

Research output: Contribution to journalArticlepeer-review


Presenilin-1 (PSEN-1) is a component of the γ-secretase complex involved in β-amyloid precursor protein (βAPP) processing. To date about 140 pathogenic mutations in the PSEN-1 gene have been identified and their main biochemical effect is to increase the production of the fibrillogenic peptide Aβ(1-42). An exception is the PSEN-1 [E318G] mutation that does not alter Aβ(1-42) generation and is generally considered a non-pathogenic polymorphism. Nevertheless, this mutation was reported to be a genetic risk factor for familial Alzheimer's disease (FAD) in the Australian population. To independently confirm this indication, we performed a case-control association study in the Italian population. We found a significant association (p <0.05, Fisher's exact test) between the presence of PSEN-1 [E318G] and FAD. In addition, on measuring the Aβ(1-42) and Aβ(1-40) concentrations in fibroblast-conditioned media cultured from PSEN-1 [E318G] carriers and PSEN-1 [wild type] controls we noted a significant decrease (p <0.05, Mann-Whitney test) in the Aβ(1-42)/Aβ(1-40) ratio in PSEN-1 [E318G] carriers, suggesting a peculiar biochemical effect of this mutation.

Original languageEnglish
Pages (from-to)1682-1688
Number of pages7
JournalNeurobiology of Aging
Issue number11
Publication statusPublished - Nov 2007


  • Amyloid beta-protein
  • E318G mutation
  • Familial Alzheimer's Disease
  • Genetics
  • Neurodegenerative disease
  • Presenilin-1
  • Skin biopsy

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)


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