title: A panel of nine cerebrospinal fluid biomarkers may identify patients with atypical parkinsonian syndromes.
abstract: BACKGROUND
  Patients presenting with parkinsonian syndromes share many clinical features, which can make diagnosis difficult. This is important as atypical parkinsonian syndromes (APSs) such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS) carry a poor prognosis, compared with patients with Parkinson's disease (PD). In addition, there is overlap between APS and dementia diseases, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD).
  
  
  OBJECTIVE
  To use a panel of cerebrospinal fluid (CSF) biomarkers to differentiate patients with APS from PD and dementia.
  
  
  METHODS
  A prospective cohort of 160 patients and 30 control participants were recruited from a single specialist centre. Patients were clinically diagnosed according to current consensus criteria. CSF samples were obtained from patients with clinical diagnoses of PD (n=31), PSP (n=33), CBS (n=14), MSA (n=31), AD (n=26) and FTD (n=16). Healthy, elderly participants (n=30) were included as controls. Total τ (t-τ), phosphorylated τ (p-τ), β-amyloid 1-42 (Aβ42), neurofilament light chain (NFL), α-synuclein (α-syn), amyloid precursor protein soluble metabolites α and β (soluble amyloid precursor protein (sAPP)α, sAPPβ) and two neuroinflammatory markers (monocyte chemoattractant protein-1 and YKL-40) were measured in CSF. A reverse stepwise regression analysis and the false discovery rate procedure were used.
  
  
  RESULTS
  CSF NFL (p<0.001), sAPPα (p<0.001) and a-syn (p=0.003) independently predicted diagnosis of PD versus APS. Together, these nine biomarkers could differentiate patients with PD from APS with an area under the curve of 0.95 and subtypes of APS from one another. There was good discriminatory power between parkinsonian groups, dementia disorders and healthy controls.
  
  
  CONCLUSIONS
  A panel of nine CSF biomarkers was able to differentiate APS from patients with PD and dementia. This may have important clinical utility in improving diagnostic accuracy, allowing better prognostication and earlier access to potential disease-modifying therapies.
authors.affiliation: Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: N K
authors.initials: NK
authors.lastname: Magdalinou
authors.affiliation: Department of Neurodegeneration, Dementia Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: R W
authors.initials: RW
authors.lastname: Paterson
authors.affiliation: Department of Neurodegeneration, Dementia Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Schott
authors.affiliation: Department of Neurodegeneration, Dementia Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: N C
authors.initials: NC
authors.lastname: Fox
authors.affiliation: Department of Neurodegeneration, Dementia Research Centre, UCL Institute of Neurology, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Mummery
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Bhatia
authors.affiliation: Department of Clinical Neuroscience, UCL Institute of Neurology, Royal Free Hospital, London, UK.
authors.forename: H R
authors.initials: HR
authors.lastname: Morris
authors.affiliation: Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Giunti
authors.affiliation: Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: T T
authors.initials: TT
authors.lastname: Warner
authors.affiliation: Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: de Silva
authors.affiliation: Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Lees
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Zetterberg
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015331:Cohort Studies; D003704:Dementia / Q000134:cerebrospinal fluid; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000473:pathology; D020734:Parkinsonian Disorders / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000473:pathology; D011446:Prospective Studies; D013494:Supranuclear Palsy, Progressive / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000473:pathology
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins
keywords: CORTICOBASAL DEGENERATION; CSF; PARKINSON'S DISEASE; POST MORTEM; SUPRANUCLEAR PALSY