title: Cerebrospinal fluid biomarkers can play a pivotal role in the diagnostic work up of primary progressive aphasia.
abstract: BACKGROUND
  Three variants of primary progressive aphasia (PPA) have been currently characterized: non fluent/agrammatic (nfv-PPA), semantic (sv-PPA), and logopenic variant (lv-PPA). lv-PPA is most commonly associated with Alzheimer's disease (AD), while nfv-PPA and sv-PPA are related to frontotemporal lobar degeneration.
  
  
  OBJECTIVE
  We aimed to determine whether cerebrospinal fluid (CSF) amyloid-β42 (Aβ42), total tau protein (t-tau), and phosphorylated tau (p-tau), frequently abnormal in AD, could constitute a useful tool in the PPA diagnostic work up, in order to identify subjects with an underlying AD pathology.
  
  
  METHODS
  We measured CSF biomarker levels in a group of twenty-eight patients, fourteen lv-PPA, nine nfv-PPA, and five sv-PPA.
  
  
  RESULTS
  Since there were no significant differences in any of the parameters investigated between nfv-PPA and sv-PPA, the two groups were considered as one (nfv/sv-PPA). At diagnosis, lv-PPA were older than nfv/sv-PPA patients (mean values: 70.7 versus 64.6 years, p = 0.02). CSF biomarker mean concentrations were significantly different in lv-PPA versus nfv/sv-PPA patients (p = 0.000): Aβ42 350.64 versus 661.64 ng/L; tau 631.21 versus 232.71 ng/L; p-tau 101 versus 38.21 ng/L. According to the recent AD diagnostic criteria, (Cummings et al., 2013) eleven lv-PPA and only one nfv/sv-PPA showed a liquoral pattern typical for AD. Finally lv-PPA had CSF biomarker levels very similar to a sample of 72 AD patients from our Department.
  
  
  CONCLUSIONS
  Our data showed that CSF biomarkers can easily and reliably detect those patients with language disorders due to an underlying AD pathology, thus offering the possibility of targeted therapeutic interventions. However, because of the small sample size, such analyses should be reproduced in larger populations of patients to confirm our data.
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Santangelo
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Coppi
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Ferrari
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Bernasconi
authors.affiliation: Department of Neurology, Papa Giovanni XXIII Hospital, Bergamo, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pinto
authors.affiliation: Laboraf, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Passerini
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Department of Neurology, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Magnani
mesh_terms: D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D018888:Aphasia, Primary Progressive / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D006801:Humans; D008609:Mental Status Schedule; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
keywords: CSF biomarkers; logopenic variant; non fluent-agrammatic variant; primary progressive aphasia; semantic variant