A novel pathogenic PSEN1 mutation in a family with Alzheimer's disease: Phenotypical and neuropathological features

Maura Gallo, Norina Marcello, Sabrina A M Curcio, Rosanna Colao, Silvana Geracitano, Livia Bernardi, Maria Anfossi, Gianfranco Puccio, Francesca Frangipane, Alessandra Clodomiro, Maria Mirabelli, Franca Vasso, Nicoletta Smirne, Gabriella Muraca, Raffaele Di Lorenzo, Raffaele Maletta, Enrico Ghidoni, Orso Bugiani, Fabrizio Tagliavini, Giorgio GiacconeAmalia C. Bruni

Research output: Contribution to journalArticlepeer-review


We report a novel presenilin1 (PSEN1) gene mutation (I143 V) in a four-generation family with Alzheimer's disease. Clinical, molecular, and neuropathological examinations were performed on index patient; thirteen affected subjects were also identified. The index patient presented at 55 with personality changes, apathy, reduction of verbal fluency, and temporal and spatial disorientation. At 68, she showed visual hallucinations; blurred language, and rigidity. She became bedridden and died at 75. A novel mutation at codon 143 was found in PSEN1 gene, changing isoleucine to valine. The brain showed severe atrophy of the frontal and temporal lobes. Parenchymal amyloid-β (Aβ) deposits were abundant, diffuse to grey structures and contained Aβ42, but very few Aβ40. Amyloid angiopathy was absent. Neurofibrillary changes were severe. Our study confirms that PSEN1 mutations can be associated with unusual phenotypes. The peculiarity of the age at onset (not very early), the long course, and the frontal involvement, together with the rather complete absence of Aβ40 and of amyloid angiopathy, widen the spectrum of PSEN1-linked phenotypes.

Original languageEnglish
Pages (from-to)425-431
Number of pages7
JournalJournal of Alzheimer's Disease
Issue number3
Publication statusPublished - 2011


  • Alzheimer's disease
  • neurodegeneration
  • neuropathology
  • PSEN1 mutation

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology


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