PEN-2 gene mutation in a familial Alzheimer's disease case

Carlo Sala Frigerio, Paola Piscopo, Elena Calabrese, Alessio Crestini, Lorenzo Malvezzi Campeggi, Rita Civita Di Fava, Sergio Fogliarino, Diego Albani, Gabriella Marcon, Rosella Cherchi, Rita Piras, Gianluigi Forloni, Annamaria Confaloni

Research output: Contribution to journalArticlepeer-review


Genetic evidence indicates a central role of cerebral accumulation of β-amyloid (Aβ) in the pathogenesis of Alzheimer's disease (AD). Beside presenilin 1 and 2, three other recently discovered proteins (Aph 1, PEN 2 and nicastrin) are associated with γ-secretase activity, the enzymatic complex generating Aβ. Alterations in genes encoding these proteins were candidates for a role in AD. The PEN 2 gene was examined for unknown mutations and polymorphisms in sporadic and familial Alzheimer patients. Samples from age-matched controls (n = 253), sporadic AD (SAD, n = 256) and familial AD (FAD, n = 140) were screened with DHPLC methodology followed by sequencing. Scanning the gene identified for the first time a missense mutation (D90N) in a patient with FAD. Three intronic polymorphisms were also identified, one of which had a higher presence of the mutated allele in AD subjects carrying the allele ε4 of apolipoprotein E than controls. The pathogenic role of the PEN-2 D90N mutation in AD is not clear, but the findings might lead to new studies on its functional and genetic role.

Original languageEnglish
Pages (from-to)1033-1036
Number of pages4
JournalJournal of Neurology
Issue number9
Publication statusPublished - Sep 2005


  • β-amyloid
  • γ-secretase
  • Genetics
  • Mutation

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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