Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-31T17:04:58.069Z Has data issue: false hasContentIssue false
  • English
  • Français

Use of CSF α-synuclein in the differential diagnosis between Alzheimer's disease and other neurodegenerative disorders

Published online by Cambridge University Press:  08 April 2015

Zheng-Yu Wang ,
Zhen-Min Han ,
Qi-Fei Liu ,
Wei Tang ,
Kui Ye  and
Yu-You Yao
Zheng-Yu Wang
Affiliation:
Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China
Zhen-Min Han
Affiliation:
Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China
Qi-Fei Liu
Affiliation:
Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China
Wei Tang
Affiliation:
Department of Clinical Laboratory Medicine, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China
Kui Ye
Affiliation:
Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China
Yu-You Yao*
Affiliation:
Department of Clinical Laboratory Medicine, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China
*
Correspondence should be addressed to: Yu-You Yao, M.D., Department of Clinical Laboratory Medicine, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, Anhui 230032, China. Phone: 86-551-63869179; Fax: 86-551-63869179. Email: [email protected].
Get access

Abstract

Background:

The etiology and pathogenesis of neurodegenerative disorders has yet to be elucidated, so their differential diagnosis is a challenge. This is especially true in differentiating Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson disease (PD), and multiple system atrophy (MSA).

Methods:

A total of 11 eligible articles were identified by search of electronic databases including PubMed, Springer Link, Elsevier, and the Cochrane Library, up to June 2014. In meta-analyses, standardized mean differences (SMD), with 95% confidence intervals (CI), comparing cerebrospinal fluid (CSF) measures of α-synuclein between the above conditions were calculated using random-effects models.

Results:

CSF α-synuclein concentrations were significantly higher in AD compared to DLB [SMD: 0.32, 95% CI: (0.02, 0.62), z = 2.07, P = 0.038]; PD [SMD: 0.87, 95% CI: (0.15, 1.58), z = 2.38, P = 0.017]; or MSA [SMD: 1.14, 95% CI: (0.15, 2.14), z = 2.25, P = 0.025]. However, no significant difference was found between patients with AD and neurological cognitively normal controls [SMD: 0.02, 95% CI: (−0.21, 0.24), z = 0.13, P = 0.894].

Conclusions:

Results of these meta-analysis suggest that quantification of CSF α-synuclein could help distinguish AD from other neurodegenerative disorders such as DLB, PD, or MSA.

Keywords

Alzheimer’s diseasedementia with Lewy bodiesParkinson diseasemultiple system atrophyα-synucleinmeta-analysis
Type
Review Article
Information
International Psychogeriatrics , Volume 27 , Issue 9 , September 2015 , pp. 1429 - 1438
Copyright
Copyright © International Psychogeriatric Association 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Beyer, K. (2006). Alpha-synuclein structure, posttranslational modification and alternative splicing as aggregation enhancers. Acta Neuropathologica, 112, 237–251.Google Scholar
Blennow, K., Wallin, A. and Hager, O. (1993). Low frequency of post-lumbar puncture headache in demented patients. Acta Neurologica Scandinavica, 88, 221–223.Google ScholarPubMed
Brookes, A. J. and St Clair, D. (1994). Synuclein proteins and Alzheimer's disease. Trends in Neurosciences, 17, 404–405.Google Scholar
Chen, X., de Silva, H. A., Pettenati, M. J. et al. (1995). The human NACP/alpha-synuclein gene: chromosome assignment to 4q21.3-q22 and TaqI RFLP analysis. Genomics, 26, 425–427.Google Scholar
Culvenor, J. G., McLean, C. A., Cutt, S. et al. (1999). Non-Abeta component of Alzheimer's disease amyloid (NAC) revisited. NAC and alpha-synuclein are not associated with Abeta amyloid. The American Journal of Pathology, 155, 1173–1181.Google Scholar
Egger, M., Davey Smith, G., Schneider, M. and Minder, C. (1997). Bias in meta-analysis detected by a simple, graphical test. British Medical Journal, 315, 629–634.Google Scholar
Emre, M. (2007). Treatment of dementia associated with Parkinson's disease. Parkinsonism and Related Disorders, 13, 457–461.Google Scholar
Esposito, A., Dohm, C. P., Kermer, P., Bahr, M. and Wouters, F. S. (2007). Alpha-synuclein and its disease-related mutants interact differentially with the microtubule protein tau and associate with the actin cytoskeleton. Neurobiology of Disease, 26, 521–531.CrossRefGoogle ScholarPubMed
Formichi, P., Battisti, C., Radi, E. and Federico, A. (2006). Cerebrospinal fluid tau, A beta, and phosphorylated tau protein for the diagnosis of Alzheimer's disease. Journal of Cellular Physiology, 208, 39–46.Google Scholar
George, J. M., Jin, H., Woods, W. S. and Clayton, D. F. (1995). Characterization of a novel protein regulated during the critical period for song learning in the zebra finch. Neuron, 15, 361–372.CrossRefGoogle ScholarPubMed
Goedert, M. (1999). Filamentous nerve cell inclusions in neurodegenerative diseases: tauopathies and alpha-synucleinopathies. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 354, 1101–1118.Google Scholar
Hong, Z. et al. (2010). DJ-1 and alpha-synuclein in human cerebrospinal fluid as biomarkers of Parkinson's disease. Brain, 133, 713–726.Google Scholar
Irizarry, M. C. et al. (1996). Characterization of the precursor protein of the non-A beta component of senile plaques (NACP) in the human central nervous system. Journal of Neuropathology and Experimental Neurology, 55, 889–895.Google Scholar
Irwin, D. J., White, M. T., Toledo, J. B. et al. (2012). Neuropathologic substrates of Parkinson disease dementia. Annals of Neurology, 72, 587–598.Google Scholar
Iwai, A. et al. (1995). The precursor protein of non-A beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system. Neuron, 14, 467–475.Google Scholar
Jakes, R., Spillantini, M. G. and Goedert, M. (1994). Identification of two distinct synucleins from human brain. FEBS Letters, 345, 27–32.Google Scholar
Jellinger, K. A. and Attems, J. (2008). Prevalence and impact of vascular and Alzheimer pathologies in Lewy body disease. Acta Neuropathologica, 115, 427–436.Google Scholar
Jicha, G. A., Abner, E. L., Schmitt, F. A. et al. (2012). Preclinical AD workgroup staging: pathological correlates and potential challenges. Neurobiology of Aging, 33, 622, e621–622.e616.Google Scholar
Kakimura, J., Kitamura, Y., Takata, K., Kohno, Y., Nomura, Y. and Taniguchi, T. (2001). Release and aggregation of cytochrome c and alpha-synuclein are inhibited by the antiparkinsonian drugs, talipexole and pramipexole. European Journal of Pharmacology, 417, 59–67.Google Scholar
Kapaki, E., Paraskevas, G. P., Emmanouilidou, E. and Vekrellis, K. (2013). The diagnostic value of CSF alpha-synuclein in the differential diagnosis of dementia with Lewy bodies vs. normal subjects and patients with Alzheimer's disease. PloS One, 8, e81654.Google Scholar
Kasuga, K. et al. (2010). Differential levels of alpha-synuclein, beta-amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer's disease. Journal of Neurology, Neurosurgery, and Psychiatry, 81, 608–610.Google Scholar
Kholodilov, N. G. et al. (1999). Increased expression of rat synuclein in the substantia nigra pars compacta identified by mRNA differential display in a model of developmental target injury. Journal of Neurochemistry, 73, 2586–2599.Google Scholar
Lavedan, C. (1998). The synuclein family. Genome Research, 8, 871–880.Google Scholar
Marti, M. J., Tolosa, E. and Campdelacreu, J. (2003). Clinical overview of the synucleinopathies. Movement Disorders: Official Journal of the Movement Disorder Society, 18 (Suppl. 6), S21–S27.Google Scholar
McKeith, I. (2004). Dementia with Lewy bodies. Dialogues in Clinical Neuroscience, 6, 333–341.Google Scholar
Mizuno, Y. et al. (1998). Mitochondrial dysfunction in Parkinson's disease. Annals of Neurology, 44, S99–S109.Google Scholar
Mollenhauer, B. et al. (2005). Tau protein, abeta 42 and S-100B protein in cerebrospinal fluid of patients with dementia with Lewy bodies. Dementia and Geriatric Cognitive Disorders, 19, 164–170.CrossRefGoogle 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, 315–325.Google Scholar
Mollenhauer, B. et al. (2011). Alpha-synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study. Lancet Neurology, 10, 230–240.Google Scholar
Noguchi-Shinohara, et al. (2009). CSF alpha-synuclein levels in dementia with Lewy bodies and Alzheimer's disease. Brain Research, 1251, 1–6.Google Scholar
Ostrerova, N. et al. (1999). Alpha-synuclein shares physical and functional homology with 14-3-3 proteins. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 19, 5782–5791.Google Scholar
Parnetti, L., Chiasserini, D., Bellomo, G. et al. (2011). Cerebrospinal fluid Tau/alpha-synuclein ratio in Parkinson's disease and degenerative dementias. Movement Disorders: Official Journal of the Movement Disorder Society, 26, 1428–1435.Google Scholar
Parnetti, L., Lanari, A., Amici, S., Gallai, V., Vanmechelen, E. and Hulstaert, F. (2001). Phospho-tau international study group. CSF phosphorylated tau is a possible marker for discriminating Alzheimer's disease from dementia with Lewy bodies, phospho-tau international study group. Journal of the Neurological Sciences, 22, 77–78.Google Scholar
Petersen, R. C. et al. (2009). Mild cognitive impairment: ten years later. Archives of Neurology, 66, 1447–1455.Google Scholar
Santacruz, K. S. and Swagerty, D. (2001). Early diagnosis of dementia. American Family Physician, 63, 703–714.Google Scholar
Shi, M. et al. (2011). Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Annals of Neurology, 69, 570–580.Google Scholar
Souza, J. M., Giasson, B. I., Lee, V. M. and Ischiropoulos, H. (2000). Chaperone-like activity of synucleins. FEBS Letters, 474, 116–119.Google Scholar
Spies, P. E., Melis, R. J., Sjogren, M. J., Rikkert, M. G. and Verbeek, M. M. (2009). Cerebrospinal fluid alpha-synuclein does not discriminate between dementia disorders. Journal of Alzheimer's Disease, 16, 363–369.Google Scholar
Spillantini, M. G., Divane, A. and Goedert, M. (1995). Assignment of human alpha-synuclein (SNCA) and beta-synuclein (SNCB) genes to chromosomes 4q21 and 5q35. Genomics, 27, 379–381.Google Scholar
Stefanis, L., Kholodilov, N., Rideout, H. J., Burke, R. E. and Greene, L. A. (2001). Synuclein-1 is selectively up-regulated in response to nerve growth factor treatment in PC12 cells. Journal of Neurochemistry, 76, 1165–1176.Google Scholar
Stewart, T., Liu, C. Q., Carmen, G. et al. (2014). Cerebrospinal fluida-synuclein predicts cognitive decline in Parkinson disease progression in the DATATOP cohort. The American Journal of Pathology, 184, 966–975.Google Scholar
Tang, W., Huang, Q., Wang, Y., Wang, Z. Y. and Yao, Y. Y. (2014a). Does CSF p-tau181 help to discriminate Alzheimer's disease from other dementias and mild cognitive impairment? A meta-analysis of the literature. Journal of Neural Transmission, 121, 1541–1553.CrossRefGoogle ScholarPubMed
Tang, W., Huang, Q., Wang, Y., Wang, Z. Y. and Yao, Y. Y. (2014b). Does CSF Aβ42 as an aid to discriminating Alzheimer's disease from other dementias and mild cognitive impairment: a meta-analysis of 50 studies. Journal of the Neurological Sciences, 345, 26–36.Google Scholar
Tateno, F., Sakakibara, R., Kawai, T., Kishi, M. and Murano, T. (2012). Alpha-synuclein in the cerebrospinal fluid differentiates synucleinopathies (Parkinson disease, dementia with Lewy bodies, multiple system atrophy) from Alzheimer disease. Alzheimer Disease and Associated Disorders, 26, 213–216.Google Scholar
Tokuda, T., Qureshi, M. M., Ardah, M. T. et al. (2010). Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease. Neurology, 75, 1766–1772.Google Scholar
Ueda, K., Fukushima, H., Masliah, E. et al. (1993). Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America, 90, 11282–11286.Google Scholar
van der Putten, H., Wiederhold, K. H., Probst, A. et al. (2000). Neuropathology in mice expressing human alpha-synuclein. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience, 20, 6021–6029.Google Scholar
Wennstrom, M., Londos, E., Minthon, L. and Nielsen, H. M. (2012). Altered CSF orexin and alpha-synuclein levels in dementia patients. Journal of Alzheimer's disease, 29, 125–132.Google Scholar