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.