The novel PSEN1 M84V mutation associated to frontal dysexecutive syndrome, spastic paraparesis, and cerebellar atrophy in a dominant Alzheimer's disease family

Maura Gallo, Francesca Frangipane, Chiara Cupidi, Matteo De Bartolo, Sabina Turone, Camilla Ferrari, Benedetta Nacmias, Giuliana Grimaldi, Valentina Laganà, Rosanna Colao, Livia Bernardi, Maria Anfossi, Maria Elena Conidi, Franca Vasso, Sabrina Anna Maria Curcio, Maria C. Mirabelli, Nicoletta Smirne, Giusi Torchia, Maria Gabriella Muraca, Gianfranco PuccioRaffaele Di Lorenzo, Maristella Piccininni, Andrea Tedde, Raffaele Giovanni Maletta, Sandro Sorbi, Amalia Cecilia Bruni

Research output: Contribution to journalArticlepeer-review

Abstract

We identified the novel PSEN1 pathogenic mutation M84V in 3 patients belonging to a large kindred affected by autosomal dominant Alzheimer's disease (AD). The clinical phenotype was characterized by early onset dementia in 14 affected subjects over 3 generations. Detailed clinical, imaging and genetic assessment was performed. We highlighted the presence of unusual symptoms such as frontal executive syndrome, psychosis and spastic paraparesis in these patients. Spastic paraparesis has been reported in other PSEN1 mutations in adjacent codons, suggesting that the position of the genetic defect may affect the clinical expression, although this phenotype can occur in mutations throughout the whole PSEN1 gene. Brain magnetic resonance imaging showed diffuse cortical atrophy, but also atrophy of cerebellar lobules, mainly involving Crus I, in 2 patients without cerebellar motor deficits. These neuroimaging results were consistent with recent findings about the association between sporadic AD and distinct and circumscribed cerebellar atrophy. The present work acknowledged the novel PSEN1 pathogenic mutation M84V and might contribute to the ongoing debate about the involvement of cerebellum in AD.

Original languageEnglish
JournalNeurobiology of Aging
DOIs
Publication statusE-pub ahead of print - May 2017

Keywords

  • Alzheimer's disease
  • Cerebellum
  • M84V
  • Presenilin 1 mutation
  • Spastic paraparesis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology
  • Clinical Neurology

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