title: Cerebrospinal-fluid Alzheimer's Disease Biomarkers and Blood-Brain Barrier Integrity in a Natural Population of Cognitive Intact Parkinson's Disease Patients.
abstract: BACKGROUND
  Cerebrospinal-fluid (CSF) Alzheimer's Disease (AD) biomarkers have been extensively studied in Parkinson's Disease (PD). Although reduced CSF beta-amyloid1-42 (Aβ42) levels have been associated with cognitive decline in PD, the alteration of CSF tau proteins remains controversial. In addition, the impairment of the blood-brain barrier (BBB) has been previously demonstrated along the PD progression.
  
  
  OBJECTIVE
  The aim of the present study was to assess CSF AD biomarkers and BBB integrity in a natural cohort of cognitive intact PD patients compared to matched controls.
  
  
  METHODS
  We measured and correlated CSF AD biomarkers and CSF/serum albumin ratio (expression of BBB integrity) in 124 PD patients and 46 controls. We distributed PD patients in three subgroups based on the Hoehn and Yahr (H&Y) staging: mild PD (1-1.5, n=40); moderate PD (2-2.5, n=58); advanced PD (3-5, n=26). PD patients were also distinguished as tremor dominant (TD, n=44) and non-tremor dominant (NTD, n=80).
  
  
  RESULTS
  PD patients showed lower CSF Aβ42 levels and higher CSF/serum albumin ratio compared to controls. CSF total tau (t-tau) concentrations as well as the CSF/serum albumin ratio gradually increased among H&Y stages. Conversely, we did not find differences between TD and NTD patients. Significantly, we documented the positive correlation between CSF t-tau levels and both CSF/serum albumin ratio and motor impairment in PD patients.
  
  
  CONCLUSIONS
  This study performed in cognitive intact PD patients confirms the progressive increase of CSF tau proteins levels and BBB impairment along with the evolution of PD pathology. Since the BBB ensures the clearance of tau proteins from brain, we hypothesize that the dysfunction of the BBB throughout the disease progression may possibly cause the concurrent increase of CSF tau proteins levels in PD, which could be irrespective of cognitive decline.
authors.affiliation: Department of Systems Medicine, Neurophysiopathology Unit, University of Rome "Tor Vergata", Rome. Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Liguori
authors.affiliation: Department of Systems Medicine, Movement Disorders Centre, University of Rome "Tor Vergata", Rome. Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Olivola
authors.affiliation: Department of Systems Medicine, Movement Disorders Centre, University of Rome "Tor Vergata", Rome. Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Pierantozzi
authors.affiliation: Department of Systems Medicine, Movement Disorders Centre, University of Rome "Tor Vergata", Rome. Italy.
authors.forename: Rocco
authors.initials: R
authors.lastname: Cerroni
authors.affiliation: Neurocenter of Southern Switzerland, Lugano. Swaziland.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Galati
authors.affiliation: Department of Systems Medicine, Movement Disorders Centre, University of Rome "Tor Vergata", Rome. Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Saviozzi
authors.affiliation: IRCCS Fondazione Santa Lucia, Rome. Italy.
authors.forename: Nicola Biagio
authors.initials: NB
authors.lastname: Mercuri
authors.affiliation: Movement Disorders Centre, Department of Systems Medicine, University of Rome "Tor Vergata", Viale Oxford, 81, 00133, Rome. Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Stefani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid / Q000150:complications / Q000473:pathology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011569:Psychiatric Status Rating Scales; 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
keywords: Blood-brain barrier; Parkinson's disease; cerebrospinal-fluid; motor impairment; tau proteins