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Published in: Journal of Neuroinflammation 1/2012

Open Access 01-12-2012 | Short report

Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease

Authors: Valerio Pisani, Alessandro Stefani, Mariangela Pierantozzi, Silvia Natoli, Paolo Stanzione, Diego Franciotta, Antonio Pisani

Published in: Journal of Neuroinflammation | Issue 1/2012

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Abstract

Background

Alterations in blood–brain barrier permeability have been proposed to represent a relevant factor contributing to Parkinson’s disease progression. However, few studies have addressed this issue in patients at different stages of disease.

Methods

Albumin was measured in cerebrospinal fluid and serum samples obtained from 73 non-demented subjects with idiopathic Parkinson’s disease and 47 age-matched control subjects. The albumin ratio (AR) was calculated to assess blood-cerebrospinal fluid and blood–brain barrier function. The group of patients with Parkinson’s disease included 46 subjects with Hoehn-Yahr staging between 1 and 2 and 27, with a score ranging from 2.5 to 4.

Results

Statistically significant differences in albumin ratio were found between patients with advanced disease, and both early-stage and unaffected groups. Conversely, early-phase patients did not differ from healthy subjects. Additionally, dopaminergic treatment seems to exert a possible effect on AR values.

Conclusions

Our study demonstrates that possible dysfunction of the blood-cerebrospinal fluid barrier, blood–brain barrier, or both, characterize Parkinson’s disease progression. The associations between clinical scores, treatments and biochemical findings suggest a progressive impairment of barrier integrity during the course of the disease.
Literature
1.
go back to reference Weiss N, Miller F, Cazaubon S, Couraud PO: The blood–brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta 2009, 1788:842–857.CrossRefPubMed Weiss N, Miller F, Cazaubon S, Couraud PO: The blood–brain barrier in brain homeostasis and neurological diseases. Biochim Biophys Acta 2009, 1788:842–857.CrossRefPubMed
2.
go back to reference Hirsch EC, Hunot S: Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol 2009, 8:382–397.CrossRefPubMed Hirsch EC, Hunot S: Neuroinflammation in Parkinson’s disease: a target for neuroprotection? Lancet Neurol 2009, 8:382–397.CrossRefPubMed
3.
go back to reference Kortekaas R, Leenders KL, van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, Hendrikse NH: Blood–brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol 2005, 57:176–179.CrossRefPubMed Kortekaas R, Leenders KL, van Oostrom JC, Vaalburg W, Bart J, Willemsen AT, Hendrikse NH: Blood–brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol 2005, 57:176–179.CrossRefPubMed
4.
go back to reference Carvey PM, Zhao CH, Hendey B, Lum H, Trachtenberg J, Desai BS, Snyder J, Zhu YG, Ling ZD: 6-Hydroxydopamine-induced alterations in blood–brain barrier permeability. Eur J Neurosci 2005, 22:1158–1168.CrossRefPubMed Carvey PM, Zhao CH, Hendey B, Lum H, Trachtenberg J, Desai BS, Snyder J, Zhu YG, Ling ZD: 6-Hydroxydopamine-induced alterations in blood–brain barrier permeability. Eur J Neurosci 2005, 22:1158–1168.CrossRefPubMed
5.
go back to reference Westin JE, Lindgren HS, Gardi J, Nyengaard JR, Brundin P, Mohapel P, Cenci MA: Endothelial proliferation and increased blood–brain barrier permeability in the basal ganglia in a rat model of 3,4-dihydroxyphenyl-L-alanine-induced dyskinesia. J Neurosci 2006, 26:9448–9461.CrossRefPubMed Westin JE, Lindgren HS, Gardi J, Nyengaard JR, Brundin P, Mohapel P, Cenci MA: Endothelial proliferation and increased blood–brain barrier permeability in the basal ganglia in a rat model of 3,4-dihydroxyphenyl-L-alanine-induced dyskinesia. J Neurosci 2006, 26:9448–9461.CrossRefPubMed
7.
go back to reference Teunissen CE, Petzold A, Bennett JL, Berven FS, Brundin L, Comabella M, Franciotta D, Frederiksen JL, Fleming JO, Furlan R, Hintzen RQ, Hughes SG, Johnson MH, Krasulova E, Kuhle J, Magnone MC, Rajda C, Rejdak K, Schmidt HK, van Pesch V, Waubant E, Wolf C, Giovannoni G, Hemmer B, Tumani H, Deisenhammer F: A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology 2009, 73:1914–1922.CrossRefPubMedPubMedCentral Teunissen CE, Petzold A, Bennett JL, Berven FS, Brundin L, Comabella M, Franciotta D, Frederiksen JL, Fleming JO, Furlan R, Hintzen RQ, Hughes SG, Johnson MH, Krasulova E, Kuhle J, Magnone MC, Rajda C, Rejdak K, Schmidt HK, van Pesch V, Waubant E, Wolf C, Giovannoni G, Hemmer B, Tumani H, Deisenhammer F: A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology 2009, 73:1914–1922.CrossRefPubMedPubMedCentral
8.
go back to reference Reiber H: Dynamics of brain-derived proteins in cerebrospinal fluid. Clin Chim Acta 2001, 310:173–186.CrossRefPubMed Reiber H: Dynamics of brain-derived proteins in cerebrospinal fluid. Clin Chim Acta 2001, 310:173–186.CrossRefPubMed
9.
go back to reference Gibb WR, Lees AJ: The significance of the Lewy body in the diagnosis of idiopathic Parkinson’s disease. Neuropathol Appl Neurobiol 1989, 15:27–44.CrossRefPubMed Gibb WR, Lees AJ: The significance of the Lewy body in the diagnosis of idiopathic Parkinson’s disease. Neuropathol Appl Neurobiol 1989, 15:27–44.CrossRefPubMed
10.
go back to reference Evans JR, Mason SL, Williams-Gray CH, Foltynie T, Brayne C, Robbins TW, Barker RA: The natural history of treated Parkinson’s disease in an incident, community based cohort. J Neurol Neurosurg Psychiatry 2011, 82:1112–1118.CrossRefPubMed Evans JR, Mason SL, Williams-Gray CH, Foltynie T, Brayne C, Robbins TW, Barker RA: The natural history of treated Parkinson’s disease in an incident, community based cohort. J Neurol Neurosurg Psychiatry 2011, 82:1112–1118.CrossRefPubMed
11.
go back to reference Barbour R, Kling K, Anderson JP, Banducci K, Cole T, Diep L, Fox M, Goldstein JM, Soriano F, Seubert P, Chilcote TJ: Red blood cells are the major source of alpha-synuclein in blood. Neurodegener Dis 2008, 5:55–59.CrossRefPubMed Barbour R, Kling K, Anderson JP, Banducci K, Cole T, Diep L, Fox M, Goldstein JM, Soriano F, Seubert P, Chilcote TJ: Red blood cells are the major source of alpha-synuclein in blood. Neurodegener Dis 2008, 5:55–59.CrossRefPubMed
12.
go back to reference McGeer PL, Itagaki S, Boyes BE, McGeer EG: Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 1988, 38:1285–1291.CrossRefPubMed McGeer PL, Itagaki S, Boyes BE, McGeer EG: Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 1988, 38:1285–1291.CrossRefPubMed
13.
go back to reference L’Episcopo F, Tirolo C, Testa N, Caniglia S, Morale MC, Cossetti C, D’Adamo P, Zardini E, Andreoni L, Ihekwaba AE, Serra PA, Franciotta D, Martino G, Pluchino S, Marchetti B: Reactive astrocytes and Wnt/β-catenin signaling link nigrostriatal injury to repair in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. Neurobiol Dis 2011, 41:508–527.CrossRefPubMed L’Episcopo F, Tirolo C, Testa N, Caniglia S, Morale MC, Cossetti C, D’Adamo P, Zardini E, Andreoni L, Ihekwaba AE, Serra PA, Franciotta D, Martino G, Pluchino S, Marchetti B: Reactive astrocytes and Wnt/β-catenin signaling link nigrostriatal injury to repair in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. Neurobiol Dis 2011, 41:508–527.CrossRefPubMed
14.
go back to reference Droździk M, Białecka M, Myśliwiec K, Honczarenko K, Stankiewicz J, Sych Z: Polymorphism in the P-glycoprotein drug transporter MDR1 gene: a possible link between environmental and genetic factors in Parkinson’s disease. Pharmacogenetics 2003, 13:259–263.CrossRefPubMed Droździk M, Białecka M, Myśliwiec K, Honczarenko K, Stankiewicz J, Sych Z: Polymorphism in the P-glycoprotein drug transporter MDR1 gene: a possible link between environmental and genetic factors in Parkinson’s disease. Pharmacogenetics 2003, 13:259–263.CrossRefPubMed
15.
go back to reference Hawkins RA, Mokashi A, Simpson IA: An active transport system in the blood–brain barrier may reduce levodopa availability. Exp Neurol 2005, 195:267–271.CrossRefPubMed Hawkins RA, Mokashi A, Simpson IA: An active transport system in the blood–brain barrier may reduce levodopa availability. Exp Neurol 2005, 195:267–271.CrossRefPubMed
16.
go back to reference Haussermann P, Kuhn W, Przuntek H, Muller T: Integrity of the blood-cerebrospinal fluid barrier in early Parkinson’s disease. Neurosci Lett 2001, 300:182–184.CrossRefPubMed Haussermann P, Kuhn W, Przuntek H, Muller T: Integrity of the blood-cerebrospinal fluid barrier in early Parkinson’s disease. Neurosci Lett 2001, 300:182–184.CrossRefPubMed
17.
go back to reference Fisone G, Snyder GL, Aperia A, Greengard P: Na+, K(+)-ATPase phosphorylation in the choroid plexus: synergistic regulation by serotonin/protein kinase C and isoproterenol/cAMP-PK/PP-1 pathways. Mol Med 1998, 4:258–265.PubMedPubMedCentral Fisone G, Snyder GL, Aperia A, Greengard P: Na+, K(+)-ATPase phosphorylation in the choroid plexus: synergistic regulation by serotonin/protein kinase C and isoproterenol/cAMP-PK/PP-1 pathways. Mol Med 1998, 4:258–265.PubMedPubMedCentral
18.
go back to reference Silverberg GD, Huhn S, Jaffe RA, Chang SD, Saul T, Heit G, Von Essen A, Rubenstein E: Downregulation of cerebrospinal fluid production in patients with chronic hydrocephalus. J Neurosurg 2002, 97:1271–1275.CrossRefPubMed Silverberg GD, Huhn S, Jaffe RA, Chang SD, Saul T, Heit G, Von Essen A, Rubenstein E: Downregulation of cerebrospinal fluid production in patients with chronic hydrocephalus. J Neurosurg 2002, 97:1271–1275.CrossRefPubMed
19.
go back to reference Woitalla D, Goetze O, Kim JI, Nikodem AB, Schmidt WE, Przuntek H, Muller T: Levodopa availability improves with progression of Parkinson’s disease. J Neurol 2006, 253:1221–1226.CrossRefPubMed Woitalla D, Goetze O, Kim JI, Nikodem AB, Schmidt WE, Przuntek H, Muller T: Levodopa availability improves with progression of Parkinson’s disease. J Neurol 2006, 253:1221–1226.CrossRefPubMed
Metadata
Title
Increased blood-cerebrospinal fluid transfer of albumin in advanced Parkinson’s disease
Authors
Valerio Pisani
Alessandro Stefani
Mariangela Pierantozzi
Silvia Natoli
Paolo Stanzione
Diego Franciotta
Antonio Pisani
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-9-188

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