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

Abstract We identified the novel PSEN1 pathogenic mutation M84V in three patients belonging to a large kindred affected by autosomal dominant Alzheimer’s disease. The clinical phenotype was characterized by early onset dementia in 14 affected subjects over 3 generations. Detailed clinical, imaging a...

Full description

Saved in:
Bibliographic Details
Published in:Neurobiology of aging 2017
Main Authors: Gallo, Maura, Frangipane, Francesca, Cupidi, Chiara, De Bartolo, Matteo, Turone, Sabina, Ferrari, Camilla, Nacmias, Benedetta, Grimaldi, Giuliana, Laganà, Valentina, Colao, Rosanna, Bernardi, Livia, Anfossi, Maria, Conidi, Maria Elena, Vasso, Franca, Curcio, Sabrina Anna Maria, Mirabelli, Maria, Smirne, Nicoletta, Torchia, Giusi, Muraca, Maria Gabriella, Puccio, Gianfranco, Di Lorenzo, Raffaele, Piccininni, Maristella, Tedde, Andrea, Maletta, Raffaele Giovanni, Sorbi, Sandro, Bruni, Amalia Cecilia
Format: Article
Language:English
Subjects:
Internal Medicine
Neurology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract We identified the novel PSEN1 pathogenic mutation M84V in three patients belonging to a large kindred affected by autosomal dominant Alzheimer’s disease. 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 MRI showed diffuse cortical atrophy, but also atrophy of cerebellar lobules, mainly involving Crus I, in two 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.
ISSN:0197-4580
DOI:10.1016/j.neurobiolaging.2017.04.017