Incomplete penetrance in familial Alzheimer’s disease with PSEN1 Ala260Gly mutation

I. Piaceri, A. Chiari, C. Galli, S. Bagnoli, C. Ferrari, S. Trujillo Saavedra, M. A. Molinari, G. Vinceti, S. Sorbi, B. Nacmias

Research output: Contribution to journalArticlepeer-review


Presenilin1 (PSEN1) gene is the most common known genetic cause of early-onset familial Alzheimer’s disease. We describe an Italian family with the known p.Ala260Gly mutation in PSEN1 gene. The presence of an asymptomatic 64-year-old male carrying the mutation provides evidence of a possible incomplete penetrance leading to a wider range of age at onset. In order to evaluate whether or not epigenetic modifications could contribute to the phenotypic heterogeneity, we assessed global DNA methylation levels which resulted significantly higher in the three females than in their presymptomatic brother. The study suggests that DNA methylation can contribute to slowing down or possibly protecting from the manifestation of symptoms even in monogenic diseases, emphasizing the great complexity of familial Alzheimer’s disease.

Original languageEnglish
JournalNeurological Sciences
Publication statusE-pub ahead of print - Apr 1 2020


  • cognitive reserve
  • DNA methylation
  • epigenetic
  • neurodegenerative disease
  • Presenilin mutation

ASJC Scopus subject areas

  • Dermatology
  • Clinical Neurology
  • Psychiatry and Mental health


Dive into the research topics of 'Incomplete penetrance in familial Alzheimer’s disease with PSEN1 Ala260Gly mutation'. Together they form a unique fingerprint.

Cite this