title: Frontotemporal dementia as the presenting phenotype of p.A53T mutation carriers in the alpha-synuclein gene.
abstract: The p.A53T point mutation in SNCA, the alpha-synuclein gene, has been linked to a rare dominant form of Parkinson's disease (PD).
  
  
  
  Here, we describe two apparently unrelated cases of p.A53T (G209A) SNCA mutation carriers with an atypical initial manifestation and disease course. Moreover, cerebrospinal fluid (CSF) levels of tau, p-tau and amyloid Aβ42 were measured in these patients and in an additional cohort of 5 symptomatic and 2 asymptomatic p.A53T carriers without an initial manifestation of dementia.
  
  
  
  Both patients exhibited an early onset frontal-dysexecutive dysfunction with apathy and emotional blunting resembling frontotemporal dementia (FTD). Motor symptoms typical of Parkinson's disease appeared only later in the disease course and were less prominent than cognitive ones, which included language impairment. Autonomic dysfunction and myoclonus also emerged in a more advanced disease stage. In both patients, Brain Magnetic Resonance Imaging showed fronto-temporo-parietal atrophy, and CSF analysis showed elevated tau protein levels. In contrast, tau protein levels were normal in a cohort of 7 other p.A53T mutation carriers (5 symptomatic/2 asymptomatic). A screen of Greek patients presenting with frontotemporal dementia failed to identify any additional subjects with the p.A53T SNCA mutation.
  
  
  
  Although cognitive decline has been recognized as a feature of the full-blown clinical picture of p.A53T related parkinsonism, a predominant frontotemporal dementia-like phenotype at presentation has not been previously described. This may represent a subtype of this disorder, with distinctive clinical, imaging and CSF biochemical characteristics, in which additional genetic or epigenetic factors may play a role.
authors.affiliation: 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Bougea
authors.affiliation: 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Koros
authors.affiliation: 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Department of Neurology, Philipps University, Marburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Stamelou
authors.affiliation: 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Athina
authors.initials: A
authors.lastname: Simitsi
authors.affiliation: 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Papagiannakis
authors.affiliation: 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Roubina
authors.initials: R
authors.lastname: Antonelou
authors.affiliation: Neurology Clinic, Henry Dunan Hospital, Athens, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Papadimitriou
authors.affiliation: Neurogenetics Unit, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Marianthi
authors.initials: M
authors.lastname: Breza
authors.affiliation: 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tasios
authors.affiliation: 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Stella
authors.initials: S
authors.lastname: Fragkiadaki
authors.affiliation: Nuclear Medicine Unit, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Xenia
authors.initials: X
authors.lastname: Geronicola Trapali
authors.affiliation: 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Mara
authors.initials: M
authors.lastname: Bourbouli
authors.affiliation: Neurogenetics Unit, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Koutsis
authors.affiliation: 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Sokratis G
authors.initials: SG
authors.lastname: Papageorgiou
authors.affiliation: 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kapaki
authors.affiliation: 1st Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: George P
authors.initials: GP
authors.lastname: Paraskevas
authors.affiliation: 2nd Department of Neurology, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Center of Clinical Research, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece. Electronic address: lstefanis@bioacademy.gr.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Stefanis
mesh_terms: D000328:Adult; D057180:Frontotemporal Dementia / Q000000981:diagnostic imaging* / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein
keywords: Alpha-synuclein; Dysexecutive syndrome; Frontotemporal dementia; Parkinson's disease; Tau protein