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α-synuclein antibodies recognize a protein present at lower levels in the CSF of patients with dementia with Lewy bodies

Published online by Cambridge University Press:  14 September 2009

Clive Ballard*
Affiliation:
Wolfson Centre for Age-Related Disease, King's College London, U.K.
Emma L. Jones
Affiliation:
Wolfson Centre for Age-Related Disease, King's College London, U.K.
Elisabet Londos
Affiliation:
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden
Lennart Minthon
Affiliation:
Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Sweden
Paul Francis
Affiliation:
Wolfson Centre for Age-Related Disease, King's College London, U.K.
Dag Aarsland
Affiliation:
Wolfson Centre for Age-Related Disease, King's College London, U.K. Clinical Neuroscience Research, Stavanger University Hospital, Norway
*
Correspondence should be addressed to: Professor Clive Ballard, Wolfson Centre for Age-Related Diseases, Wolfson Building, Guy's Campus, King's College London, London Bridge, SE1 1UL, U.K. Phone: +44 207 848 6568; Fax: +44 207 848 6145. Email: [email protected].
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Abstract

Background: Dementia with Lewy bodies (DLB) accounts for 15–20% of the millions of people worldwide with dementia. Accurate diagnosis is essential to avoid harm and optimize clinical management. There is therefore an urgent need to identify reliable biomarkers.

Methods: Mass spectrometry was used to determine the specificity of antibody α-synuclein (211) for α-synuclein. Using gel electrophoresis we measured protein levels detected by α-synuclein specific antibodies in the cerebrospinal fluid (CSF) of DLB patients and compared them to age matched controls.

Results: A 24 kDa band was detected using α-synuclein specific antibodies which was significantly reduced in the CSF of DLB patients compared to age matched controls (p < 0.05). Further analysis confirmed that even DLB patients with mild dementia showed significant reductions in this protein in comparison to controls.

Conclusions: The current study emphasizes the necessity for further studies of CSF α-synuclein as a biomarker of DLB and extends our previous knowledge by establishing a potential relationship between α-synuclein and the severity of cognitive impairment. The identification of this 24 kDa protein is the next important step in these studies.

Type
Research Article
Copyright
Copyright © International Psychogeriatric Association 2009

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References

Aarsland, D., Andersen, K., Larsen, J. P., Lolk, A. and Kragh-Sorensen, P. (2003) Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Archives of Neurology, 60, 387392.CrossRefGoogle ScholarPubMed
Aarsland, D. et al. . (2005). Neuroleptic sensitivity in Parkinson's disease and parkinsonian dementias. Journal of Clinical Psychiatry, 66, 633637.Google ScholarPubMed
Ballard, C. et al. (2000). Delusions associated with elevated muscarinic binding in dementia with Lewy bodies. Annals of Neurology, 48, 868876.3.0.CO;2-0>CrossRefGoogle ScholarPubMed
Boeve, B. F., Silber, M. H. and Ferman, T. J. (2004). REM sleep behavior disorder in Parkinson's disease and dementia with Lewy bodies. Journal of Geriatric Psychiatry and Neurology, 17, 146157.CrossRefGoogle ScholarPubMed
Borghi, R. et al. (2000). Full length alpha-synuclein is present in cerebrospinal fluid from Parkinson's disease and normal subjects. Neuroscience Letters, 287, 6567.CrossRefGoogle ScholarPubMed
El-Agnaf, OM. et al. (2003). α-Synuclein implicated in Parkinson's disease is present in extracellular bioloigcal fluids including human plasma. FASEB Journal, 17, 19451947.CrossRefGoogle Scholar
El-Agnaf, O. M. et al. . (2006). Detection of oligomeric forms of alpha-synuclein protein in human plasma as a potential biomarker for Parkinson's disease. FASEB Journal, 20, 419425.CrossRefGoogle ScholarPubMed
Hansen, L. et al. (1990). The Lewy body variant of Alzheimer's disease: a clinical and pathological entity. Neurology, 40, 18.CrossRefGoogle Scholar
Jakowec, M. W., Petzinger, G. M., Sastry, S., Donaldson, D. M., McCormack, A. and Langston, J. W. (1998). The native form of alpha-synuclein is not found in the cerebrospinal fluid of patients with Parkinson's disease or normal controls. Neuroscience Letters, 253, 1316.CrossRefGoogle ScholarPubMed
Lippa, C. F., Smith, T. W. and Perry, E. (1999). Dementia with Lewy bodies: choline acetyltransferase parallels nucleus basalis pathology. Journal of Neural Transmission, 106, 525535.CrossRefGoogle ScholarPubMed
McKeith, I. G. et al. (1996). Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology, 47, 11131124.CrossRefGoogle Scholar
McKeith, I. et al. (2004). International Psychogeriatric Association Expert Meeting on DLB: dementia with Lewy bodies. Lancet Neurology, 3, 1928.Google ScholarPubMed
McKeith, I. G. et al. (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology, 65, 18631872.CrossRefGoogle ScholarPubMed
McKeith, I. et al. (2007). Sensitivity and specificity of dopamine transporter imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III multicentre study. Lancet Neurology, 6, 305313.CrossRefGoogle ScholarPubMed
Mollenhauer, B. (2006). Quantification of a α-synuclein in cerebrospinal fluid: implications for a biomarker for Dementia with Lewy Bodies and Parkinson's Disease. Paper presented to the 4th International Workshop on DLB and PDD, Yokohama, Japan. Available at http://www.secretariat.ne.jp/dlb2006.Google Scholar
Mollenhauer, B. et al. (2008). Direct quantification of CSF alpha-synuclein by ELISA and first cross-sectional study in patients with neurodegeneration. Experimental Neurology, 213, 315325.CrossRefGoogle ScholarPubMed
Mukaetova-Ladinska, E. B. et al. (2008). Alpha- and gamma-synuclein proteins are present in cerebrospinal fluid and are increased in aged subjects with neurodegenerative and vascular changes. Dementia and Geriatric Cognitive Disorders, 26 3242.CrossRefGoogle ScholarPubMed
Reid, W. G. J. et al. (1996). A longitudinal study of Parkinson's disease: clinical and neuropsychological correlates of dementia. Journal of Clinical Neuroscience, 3, 327333.CrossRefGoogle ScholarPubMed
Tiraboschi, P., Salmon, D. P., Hansen, L. A., Hofstetter, R. C., Thal, L. J. and Corey-Bloom, J. (2006). What best differentiates Lewy body from Alzheimer's disease in early-stage dementia? Brain, 129, 729735.CrossRefGoogle ScholarPubMed
Tokuda, T. et al. (2006). Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson's disease. Biochemical and Biophysical Research Communications, 349, 162166.CrossRefGoogle ScholarPubMed