title: Cerebrospinal fluid biomarkers in the differential diagnosis of Alzheimer's disease from other cortical dementias.
abstract: BACKGROUND
  Considering that most semantic dementia (SD) and frontotemporal dementia (FTD) patients show no post-mortem Alzheimer's disease (AD) pathology, cerebrospinal fluid (CSF) biomarkers may be of value for distinguishing these patients from those with AD. Additionally, biomarkers may be useful for identifying patients with atypical phenotypic presentations of AD, such as posterior cortical atrophy (PCA) and primary progressive non-fluent or logopenic aphasia (PNFLA).
  
  
  METHODS
  The authors investigated CSF biomarkers (beta-amyloid 1-42 (Aβ(42)), total tau (T-tau) and phosphorylated tau (P-tau)) in 164 patients with AD (n=60), PCA (n=15), behavioural variant FTD (n=27), SD (n=19), PNFLA (n=26) and functional cognitive disorders (FCD, n=17). The authors then examined the diagnostic value of these CSF biomarkers in distinguishing these patients from those with AD.
  
  
  RESULTS
  The P-Tau/Aβ(42) ratio was found to be the best biomarker for distinguishing AD from FTD and SD, with a sensitivity of 91.7% and 98.3%, respectively, and a specificity of 92.6% and 84.2%, respectively. As expected, biomarkers were less effective in differentiating AD from PNFLA and PCA, as significant proportions of PCA and PNFLA patients (60% and 61.5%, respectively) had concurrent alterations of both T-tau/Aβ(42) and P-Tau/Aβ(42) ratios. None of the FCD patients had a typical AD CSF profile or abnormal T-tau/Aβ(42) or P-Tau/Aβ(42) ratios.
  
  
  CONCLUSIONS
  The P-Tau/Aβ(42) ratio is a useful tool to distinguish AD from both FTD and SD, which are known to involve pathological processes distinct from AD. Biomarkers could be useful for identifying patients with an atypical AD phenotype that includes PNFLA and PCA.
authors.affiliation: CRICM, UPMC Univ Paris 06, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Leonardo Cruz
authors.initials: LC
authors.lastname: de Souza
authors.forename: Foudil
authors.initials: F
authors.lastname: Lamari
authors.forename: Serge
authors.initials: S
authors.lastname: Belliard
authors.forename: Claude
authors.initials: C
authors.lastname: Jardel
authors.forename: Caroline
authors.initials: C
authors.lastname: Houillier
authors.forename: Raphael
authors.initials: R
authors.lastname: De Paz
authors.forename: Bruno
authors.initials: B
authors.lastname: Dubois
authors.forename: Marie
authors.initials: M
authors.lastname: Sarazin
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D018888:Aphasia, Primary Progressive / Q000134:cerebrospinal fluid / Q000175:diagnosis; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002540:Cerebral Cortex / Q000473:pathology; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000175:diagnosis; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D003937:Diagnosis, Differential; D005260:Female; D057180:Frontotemporal Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis; D006801:Humans; D008297:Male; 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; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins