Increased levels of CSF total but not oligomeric or phosphorylated forms of alpha-synuclein in patients diagnosed with probable Alzheimer’s disease
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Several studies reported an association between CSF alpha-synuclein (α-syn) and tau in Alzheimer’s disease (AD), and demonstrated the significance of α-syn in improving the diagnostic sensitivity/specificity of classical AD CSF biomarkers. In the current study, we measured CSF levels of different α-syn species in a cohort of AD patients (n = 225) who showed a CSF profile typical of AD at baseline as well as in cognitively intact controls (n = 68). CSF total α-syn (t-α-syn) significantly increased in the AD group (p < 0.0001) compared to controls, while oligomeric- and phosphorylated-Ser129-α-syn did not change significantly. ROC analysis showed a sensitivity of 85% and a specificity of 84% (AUC = 0.88) in distinguishing AD from controls. T-α-syn levels correlated positively with tau species in AD group and negatively with baseline MMSE score. Our data support the added value of measurement of CSF α-syn species for further characterization of the CSF AD profile.
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Numerous studies have documented unaltered or slightly increased cerebrospinal fluid αSyn levels in patients with mild cognitive impairment and Alzheimer's disease.
“numerous studies have documented unaltered or slightly increased CSF αSyn levels in patients with MCI and AD [27, 80–82, 86, 90, 91, 93, 94].”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [93]
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1 retracted
RETRACTED: Soluble α-Synuclein Is a Novel Modulator of Alzheimer's Disease Pathophysiology
Larson, M. E., Sherman, M. A., Greimel, S., Kuskowski, M., Schneider, J. A., Bennett, D. A., & Lesné, S. E. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.0581-12.2012 · Cited by 128 · see citing works
RetractedpROC: an open-source package for R and S+ to analyze and compare ROC curves
Robin, X., Turck, N., Hainard, A., Tiberti, N., Lisacek, F., Sanchez, J.-C., & Müller, M. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-77 · Cited by 13,697 · see citing works
Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria
Dubois, B., Feldman, H. H., Jacova, C., DeKosky, S. T., Barberger-Gateau, P., Cummings, J., Delacourte, A., Galasko, D., Gauthier, S., Jicha, G., et al. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70178-3 · Cited by 4,411 · see citing works
α-Synuclein is phosphorylated in synucleinopathy lesions
Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M., Shen, J., Takio, K., & Iwatsubo, T. (2002) · Nature Cell Biology · doi:10.1038/ncb748 · Cited by 1,906 · see citing works
Cerebrospinal fluid and plasma biomarkers in Alzheimer disease
Blennow, K., Hampel, H., Weiner, M., & Zetterberg, H. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.4 · Cited by 1,863 · see citing works
In vivo demonstration that α-synuclein oligomers are toxic
Winner, B., Jappelli, R., Maji, S. K., Desplats, P., Boyer, L. F., Aigner, S., Hetzer, C., Loher, T., Vilar, M., Campioni, S., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100976108 · Cited by 1,487 · see citing works
Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease.
Uéda, K., Fukushima, H., Masliah, E., Xia, Y., Iwai, A., Yoshimoto, M., Otero, D. A., Kondo, J. D. M., Ihara, Y., & Saitoh, T. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.11282 · Cited by 1,469 · see citing works
Anderson, J. P., Walker, D., Goldstein, J. M., de Laat, R., Banducci, K., Caccavello, R. J., Barbour, R., Huang, J., Kling, K., Lee, M., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600933200 · Cited by 1,418 · see citing works
A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking
Teunissen, C. E., Petzold, A., Bennett, J. L., Berven, F. S., Brundin, L., Comabella, M., Franciotta, D., Frederiksen, J. L., Fleming, J. O., Furlan, R., et al. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c47cc2 · Cited by 845 · see citing works
DJ-1 and α-synuclein in human cerebrospinal fluid as biomarkers of Parkinson’s disease
Hong, Z., Shi, M., Chung, K. A., Quinn, J. F., Peskind, E. R., Galasko, D., Jankovic, J., Zabetian, C. P., Leverenz, J. B., Baird, G., et al. (2010) · Brain · doi:10.1093/brain/awq008 · Cited by 615 · see citing works
Red Blood Cells Are the Major Source of Alpha-Synuclein in Blood
Barbour, R., Kling, K., Anderson, J. P., Banducci, K., Cole, T. A., Diep, L., Fox, M., Goldstein, J. M., Soriano, F., Seubert, P. A., et al. (2008) · Neurodegenerative Diseases · doi:10.1159/000112832 · Cited by 527 · see citing works
Detection of elevated levels of α-synuclein oligomers in CSF from patients with Parkinson disease
Tokuda, T., Qureshi, M. M., Ardah, M. T., Varghese, S., Shehab, S. A. S., Kasai, T., Ishigami, N., Tamaoka, A., Nakagawa, M., & El‐Agnaf, O. M. A. (2010) · Neurology · doi:10.1212/wnl.0b013e3181fd613b · Cited by 526 · see citing works
Self-citationThe α‐Synucleinopathies: Parkinson's Disease, Dementia with Lewy Bodies, and Multiple System Atrophy
Spillantini, M. G., & Goedert, M. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06900.x · Cited by 520 · see citing works
Pathological roles of α-synuclein in neurological disorders
Vekrellis, K., Xilouri, M., Emmanouilidou, E., Rideout, H. J., & Stefanis, L. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70213-7 · Cited by 359 · see citing works
Eusebi, P. (2013) · Cerebrovascular Diseases · doi:10.1159/000353863 · Cited by 316 · see citing works
Self-citationPhosphorylated α-Synuclein in Parkinson’s Disease
Wang, Y., Shi, M. Y., Chung, K. A., Zabetian, C. P., Leverenz, J. B., Berg, D., Srulijes, K., Trojanowski, J. Q., Lee, V. M. ‐., Siderowf, A. D., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3002566 · Cited by 281 · see citing works
Oligomeric and phosphorylated alpha-synuclein as potential CSF biomarkers for Parkinson’s disease
Majbour, N. K., Vaikath, N. N., van Dijk, K. D., Ardah, M. T., Varghese, S., Vesterager, L. B., Montezinho, L. P., Poole, S., Safieh‐Garabedian, B., Tokuda, T., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0072-9 · Cited by 279 · see citing works
Self-citationPaleologou, K. E., Kragh, C. L., Mann, D. M. A., Salem, S. A., Al‐Shami, R., Allsop, D., Hassan, A. H. M., Jensen, P. H., & El‐Agnaf, O. M. A. (2008) · Brain · doi:10.1093/brain/awn349 · Cited by 225 · see citing works
Self-citationHansson, O., Hall, S., Öhrfelt, A., Zetterberg, H., Blennow, K., Minthon, L., Nägga, K., Londos, E., Varghese, S., Majbour, N. K., et al. (2014) · Alzheimer s Research & Therapy · doi:10.1186/alzrt255 · Cited by 208 · see citing works
Self-citationSkillbäck, T., Rosén, C., Asztely, F., Mattsson, N., Blennow, K., & Zetterberg, H. (2014) · JAMA Neurology · doi:10.1001/jamaneurol.2013.6455 · Cited by 207 · see citing works
Cerebrospinal fluid α-synuclein in neurodegenerative disorders—A marker of synapse loss?
Öhrfelt, A., Grognet, P., Andreasen, N., Wallin, A., Vanmechelen, E., Blennow, K., & Zetterberg, H. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.11.015 · Cited by 198 · see citing works
Cerebrospinal fluid Tau/α‐synuclein ratio in Parkinson's disease and degenerative dementias
Parnetti, L., Chiasserini, D., Bellomo, G., Giannandrea, D., Carlo, C. D., Qureshi, M. M., Ardah, M. T., Varghese, S., Bonanni, L., Borroni, B., et al. (2011) · Movement Disorders · doi:10.1002/mds.23670 · Cited by 170 · see citing works
Self-citationMagnoni, S., Esparza, T. J., Conte, V., Carbonara, M., Carrabba, G. G., Holtzman, D. M., Zipfel, G. J., Stocchetti, N., & Brody, D. L. (2011) · Brain · doi:10.1093/brain/awr286 · Cited by 170 · see citing works
Teunissen, C. E., Petzold, A., Bennett, J. L., Berven, F. S., Brundin, L., Comabella, M., Franciotta, D. M., Federiksen, J. L., Fleming, J. O., Furlan, R., et al. (2010) · Journal of Laboratory Medicine · doi:10.1515/jlm.2010.001 · Cited by 162 · see citing works
Vaikath, N. N., Majbour, N. K., Paleologou, K. E., Ardah, M. T., van Dam, E., van de Berg, W. D. J., Forrest, S. L., Parkkinen, L., Gai, W., Hattori, N., et al. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.04.009 · Cited by 142 · see citing works
Self-citationKasuga, K., Tokutake, T., Ishikawa, A., Uchiyama, T., Tokuda, T., Onodera, O., Nishizawa, M., & Ikeuchi, T. (2010) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2009.197483 · Cited by 142 · see citing works
Self-citationParnetti, L., Chiasserini, D., Eusebi, P., Giannandrea, D., Bellomo, G., Carlo, C. D., Padiglioni, C., Mastrocola, S., Lisetti, V., & Calabresi, P. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-111349 · Cited by 109 · see citing works
Self-citationToledo, J. B., Korff, A., Shaw, L. M. J., Trojanowski, J. Q., & Zhang, J. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1148-z · Cited by 106 · see citing works
α-Synuclein in Cerebrospinal Fluid of Alzheimer's Disease and Mild Cognitive Impairment
Korff, A., Liu, C., Ginghina, C., Shi, M., Zhang, J., & Initiative, F. T. A. D. N. (2013) · Journal of Alzheimer’s Disease · doi:10.3233/jad-130458 · Cited by 95 · see citing works
Increased CSF α‐synuclein levels in Alzheimer's disease: Correlation with tau levels
Slaets, S., Vanmechelen, E., Le Bastard, N., Decraemer, H., Vandijck, M., Martin, J., De Deyn, P. P., & Engelborghs, S. (2014) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2013.10.004 · Cited by 85 · see citing works
CSF α-Synuclein Does Not Discriminate Dementia with Lewy Bodies from Alzheimer's Disease
Reesink, F. E., Lemstra, A. W., van Dijk, K. D., Berendse, H. W., van de Berg, W. D. J., Klein, M., Blankenstein, M. A., Scheltens, P., Verbeek, M. M., & van der Flier, W. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100186 · Cited by 84 · see citing works
Kapaki, E. N., Paraskevas, G. P., Emmanouilidou, E., & Vekrellis, K. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081654 · Cited by 79 · see citing works
Increased α-synuclein levels in the cerebrospinal fluid of patients with Creutzfeldt–Jakob disease
Kasai, T., Tokuda, T., Ishii, R., Ishigami, N., Tsuboi, Y., Nakagawa, M., Mizuno, T., & El‐Agnaf, O. M. A. (2014) · Journal of Neurology · doi:10.1007/s00415-014-7334-7 · Cited by 34 · see citing works
Self-citationWang, H., Wang, K. Y., Xu, W., et al. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07749.x · Cited by 31 · see citing works
Flagged first, then by citations
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- Larson M. E.. In J Neurosci Vol. 32 10253– 10266 (2012). PMC3425439 22836259
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Ashton, N. J., Janelidze, S., Al Khleifat, A., Leuzy, A., van der Ende, E. L., Karikari, T. K., Benedet, A. L., Pascoal, T. A., Lleó, A., Parnetti, L., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23620-z · Cited by 545 · see citing works
Self-citationCurrent state of Alzheimer’s fluid biomarkers
Molinuevo, J. L., Ayton, S., Batrla, R., Bednar, M. M., Bittner, T., Cummings, J., Fagan, A. M., Hampel, H., Mielke, M. M., Mikulskis, A., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1932-x · Cited by 518 · see citing works
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Shi, M., Tang, L., Toledo, J. B., Ginghina, C., Wang, H., Aro, P., Jensen, P. H., Weintraub, D., Chen‐Plotkin, A. S., Irwin, D. J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.015 · Cited by 42 · see citing works
Wang, H., Stewart, T., Toledo, J. B., Ginghina, C., Tang, L., Atik, A., Aro, P., Shaw, L. M., Trojanowski, J. Q., Galasko, D. R., et al. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-171013 · Cited by 33 · see citing works
- Authors
- Majbour, N. K., Chiasserini, D., Vaikath, N. N., Eusebi, P., Tokuda, T., van de Berg, W., Parnetti, L., Calabresi, P., & El-Agnaf, O. M. A.
- Affiliations
- Amsterdam Neuroscience (NL)
- University of Perugia (IT)
- Lund University (SE)
- Kyoto Prefectural University of Medicine (JP)
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-01-10
- Volume
- 7
- Issue
- 1
- Pages
- 40263-40263
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5223278
- OpenAlex
- W2569175784
- Cited by
- 55
- References
- 34
- Citations by year
- 2025: 10 · 2024: 4 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 9 · 2019: 7 · 2018: 7 · 2017: 2
- FWCI
- 5.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Lund University Publications (Lund University) (submittedVersion)
- PubliCatt (Università Cattolica del Sacro Cuore) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- Ministero dell’Istruzione, dell’Università e della Ricerca (PRIN 2010-2011 “, 2010-2011, (PRIN 2010), 2010PWNJXK)
- Università degli Studi di Perugia
- Japan Society for the Promotion of Science (16K14254, 15K09322)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- alpha-synuclein, cerebrospinal fluid biomarkers, Alzheimer's disease, oligomeric alpha-synuclein, phosphorylated alpha-synuclein, tau protein, sensitivity and specificity, cognitive impairment
- MeSH terms
- Aged, Alzheimer Disease, Female, Humans, Male, Middle Aged, Phosphorylation, ROC Curve, Biomarkers, tau Proteins, alpha-Synuclein
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