Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4932734 | Neurobiology of Aging | 2017 | 19 Pages |
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.
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Authors
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,