TY - JOUR
T1 - Cerebrospinal-fluid Alzheimer’s disease biomarkers and blood-brain barrier integrity in a natural population of cognitive intact Parkinson’s disease patients
AU - Liguori, Claudio
AU - Olivola, Enrica
AU - Pierantozzi, Mariangela
AU - Cerroni, Rocco
AU - Galati, Salvatore
AU - Saviozzi, Valentina
AU - Mercuri, Nicola Biagio
AU - Stefani, Alessandro
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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. Method: 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. Conclusion: 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.
AB - 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. Method: 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. Conclusion: 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.
KW - Blood-brain barrier
KW - Cerebrospinal-fluid
KW - Motor impairment
KW - Parkinson’s disease
KW - Tau proteins
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U2 - 10.2174/1871527316666161205123123
DO - 10.2174/1871527316666161205123123
M3 - Article
AN - SCOPUS:85038260326
VL - 16
SP - 339
EP - 345
JO - CNS and Neurological Disorders - Drug Targets
JF - CNS and Neurological Disorders - Drug Targets
SN - 1871-5273
IS - 3
ER -