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Cerebrospinal-fluid Alzheimer's Disease Biomarkers and Blood-Brain Barrier Integrity in a Natural Population of Cognitive Intact Parkinson's Disease Patients.
CNS Neurol Disord Drug Targets. 2017; 16(3):339-345.CN

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.

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.

Authors+Show Affiliations

Department of Systems Medicine, Neurophysiopathology Unit, University of Rome "Tor Vergata", Rome. Italy.Department of Systems Medicine, Movement Disorders Centre, University of Rome "Tor Vergata", Rome. Italy.Department of Systems Medicine, Movement Disorders Centre, University of Rome "Tor Vergata", Rome. Italy.Department of Systems Medicine, Movement Disorders Centre, University of Rome "Tor Vergata", Rome. Italy.Neurocenter of Southern Switzerland, Lugano. Swaziland.Department of Systems Medicine, Movement Disorders Centre, University of Rome "Tor Vergata", Rome. Italy.IRCCS Fondazione Santa Lucia, Rome. Italy.Movement Disorders Centre, Department of Systems Medicine, University of Rome "Tor Vergata", Viale Oxford, 81, 00133, Rome. Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27934563

Citation

Liguori, Claudio, et al. "Cerebrospinal-fluid Alzheimer's Disease Biomarkers and Blood-Brain Barrier Integrity in a Natural Population of Cognitive Intact Parkinson's Disease Patients." CNS & Neurological Disorders Drug Targets, vol. 16, no. 3, 2017, pp. 339-345.
Liguori C, Olivola E, Pierantozzi M, et al. Cerebrospinal-fluid Alzheimer's Disease Biomarkers and Blood-Brain Barrier Integrity in a Natural Population of Cognitive Intact Parkinson's Disease Patients. CNS Neurol Disord Drug Targets. 2017;16(3):339-345.
Liguori, C., Olivola, E., Pierantozzi, M., Cerroni, R., Galati, S., Saviozzi, V., Mercuri, N. B., & Stefani, A. (2017). Cerebrospinal-fluid Alzheimer's Disease Biomarkers and Blood-Brain Barrier Integrity in a Natural Population of Cognitive Intact Parkinson's Disease Patients. CNS & Neurological Disorders Drug Targets, 16(3), 339-345. https://doi.org/10.2174/1871527316666161205123123
Liguori C, et al. Cerebrospinal-fluid Alzheimer's Disease Biomarkers and Blood-Brain Barrier Integrity in a Natural Population of Cognitive Intact Parkinson's Disease Patients. CNS Neurol Disord Drug Targets. 2017;16(3):339-345. PubMed PMID: 27934563.
* Article titles in AMA citation format should be in sentence-case
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 - 2016/09/01/received PY - 2016/11/03/revised PY - 2016/11/21/accepted PY - 2016/12/10/pubmed PY - 2018/5/12/medline PY - 2016/12/10/entrez KW - Blood-brain barrier KW - Parkinson's disease KW - cerebrospinal-fluid KW - motor impairment KW - tau proteins SP - 339 EP - 345 JF - CNS & neurological disorders drug targets JO - CNS Neurol Disord Drug Targets VL - 16 IS - 3 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. SN - 1996-3181 UR - https://www.unboundmedicine.com/medline/citation/27934563/Cerebrospinal_fluid_Alzheimer's_Disease_Biomarkers_and_Blood_Brain_Barrier_Integrity_in_a_Natural_Population_of_Cognitive_Intact_Parkinson's_Disease_Patients_ L2 - https://www.ingentaconnect.com/openurl?genre=article&issn=1871-5273&volume=16&issue=3&spage=339&aulast=Liguori DB - PRIME DP - Unbound Medicine ER -