Low CSF Levels of Both α-Synuclein and the α-Synuclein Cleaving Enzyme Neurosin in Patients with Synucleinopathy
Open accessAbstract
Neurosin is a protease that in vitro degrades α-synuclein, the main constituent of Lewy bodies found in brains of patients with synucleinopathy including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Several studies have reported reduced cerebrospinal fluid (CSF) levels of α-synuclein in synucleinopathy patients and recent data also proposes a significant role of α-synuclein in the pathophysiology of Alzheimer's disease (AD). To investigate potential links between neurosin and its substrate α-synuclein in vivo we used a commercially available sandwich ELISA and an in-house developed direct ELISA to quantify CSF levels of α-synuclein and neurosin in patients diagnosed with DLB, PD and PD dementia (PDD) versus AD patients and non-demented controls. We found that patients with synucleinopathy displayed lower CSF levels of neurosin and α-synuclein compared to controls and AD patients. In contrast, AD patients demonstrated significantly increased CSF α-synuclein but similar neurosin levels compared to non-demented controls. Further, CSF neurosin and α-synuclein concentrations were positively associated in controls, PD and PDD patients and both proteins were highly correlated to CSF levels of phosphorylated tau in all investigated groups. We observed no effect of gender or presence of the apolipoprotein Eε4 allele on neither neurosin or α-synuclein CSF levels. In concordance with the current literature our study demonstrates decreased CSF levels of α-synuclein in synucleinopathy patients versus AD patients and controls. Importantly, decreased α-synuclein levels in patients with synucleinopathy appear linked to low levels of the α-synuclein cleaving enzyme neurosin. In contrast, elevated levels of α-synuclein in AD patients were not related to any altered CSF neurosin levels. Thus, altered CSF levels of α-synuclein and neurosin in patients with synucleinopathy versus AD may not only mirror disease-specific neuropathological mechanisms but may also serve as fit candidates for future biomarker studies aiming at identifying specific markers of synucleinopathy.
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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 [81]
Patients with synucleinopathies, mainly Parkinson's disease and dementia with Lewy bodies, frequently exhibit reduced levels of cerebrospinal fluid αSyn.
“patients with synucleinopathies, mainly Parkinson’s disease (PD) and DLB, frequently exhibit reduced levels of CSF αSyn [19, 79–81]”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [81]
Lower cerebrospinal fluid αSyn could distinguish Parkinson's disease from Alzheimer's disease patients.
“several studies including our own have shown that lower CSF αSyn could distinguish PD from AD patients [81, 97].”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [81]
There is a strong correlation between cerebrospinal fluid levels of αSyn and both total tau and phosphorylated tau.
“The same study further confirmed the by us and others previously reported strong correlation between CSF levels of αSyn and both t-tau and p-tau [19, 81, 98].”
From α-synuclein in the pathophysiology of Alzheimer’s disease (2019) · cites this paper as [81]
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2 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
RetractedSpencer, B. J., Michael, S., Shen, J., Kosberg, K. A., Rockenstein, E. M., Patrick, C., Adame, A., & Masliah, E. (2012) · Molecular Therapy · doi:10.1038/mt.2012.66 · Cited by 69 · see citing works
RetractedMcKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Staging of brain pathology related to sporadic Parkinson’s disease
Braak, H., Tredici, K. D., Rüb, U., de Vos, R. A. I., Jansen Steur, E. N. H., & Braak, E. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00065-9 · Cited by 10,777 · see citing works
Spillantini, M. G., Schmidt, M. L., Lee, V. M.-Y., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997) · Nature · doi:10.1038/42166 · Cited by 8,382 · see citing works
Diagnosis and management of dementia with Lewy bodies: Third report of the DLB consortium
McKeith, I. G., Dickson, D. W., Lowe, J., Emre, M., O'Brien, J. T., Feldman, H., Cummings, J., Duda, J. E., Lippa, C., Perry, E. K., et al. (2005) · Neurology · doi:10.1212/01.wnl.0000187889.17253.b1 · Cited by 5,069 · see citing works
McKeith, I. G., Galasko, D., Kosaka, K., Perry, E. K., Dickson, D. W., Hansen, L. A., Salmon, D. P., Lowe, J., Mirra, S. S., Byrne, E. J., et al. (1996) · Neurology · doi:10.1212/wnl.47.5.1113 · Cited by 3,960 · see citing works
Clinical diagnostic criteria for dementia associated with Parkinson’s disease
Emre, M., Aarsland, D., Brown, R., Burn, D. J., Duyckaerts, C., Mizuno, Y., Broe, G. A., Cummings, J., Dickson, D. W., Gauthier, S., et al. (2007) · Movement Disorders · doi:10.1002/mds.21507 · Cited by 3,027 · see citing works
Diagnostic Criteria for Parkinson Disease
Gelb, D. J., Oliver, E., & Gilman, S. (1999) · Archives of Neurology · doi:10.1001/archneur.56.1.33 · Cited by 2,822 · see citing works
Goetz, C. G., Poewe, W. H., Rascol, O., Sampaio, C., Stebbins, G. T., Counsell, C. E., Giladi, N., Holloway, R. G., Moore, C. G., Wenning, G. K., et al. (2004) · Movement Disorders · doi:10.1002/mds.20213 · Cited by 2,360 · 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
Inclusion formation and neuronal cell death through neuron-to-neuron transmission of α-synuclein
Desplats, P., Lee, H.-J., Bae, E.-J., Patrick, C., Rockenstein, E., Crews, L., Spencer, B., Masliah, E., & Lee, S.-J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903691106 · Cited by 1,485 · see citing works
The Clinical Diagnosis of Alzheimer's Disease
Wade, J. P. H., Mirsen, T. R., Hachinski, V. C., Fisman, M., Lau, C. S., & Merskey, H. (1987) · Archives of Neurology · doi:10.1001/archneur.1987.00520130016010 · Cited by 1,416 · see citing works
Fagan, A. M., Mintun, M. A., Mach, R. H., Lee, S., Dence, C. S., Shah, A. R., LaRossa, G. N., Spinner, M. L., Klunk, W. E., Mathis, C. A., et al. (2006) · Annals of Neurology · doi:10.1002/ana.20730 · Cited by 1,246 · see citing works
Emmanouilidou, E., Melachroinou, K., Roumeliotis, T., Garbis, S. D., Ntzouni, M., Margaritis, L. H., Stefanis, L., & Vekrellis, K. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5699-09.2010 · Cited by 1,115 · see citing works
Saman, S., Kim, W., Raya, M., Visnick, Y., Miro, S., Saman, S., Jackson, B., McKee, A. C., Alvarez, V. E., Lee, N. C. Y., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.277061 · Cited by 985 · see citing works
Hansen, C., Angot, E., Bergström, A.-L., Steiner, J. A., Pieri, L., Paul, G., Outeiro, T. F., Melki, R., Kallunki, P., Fog, K., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci43366 · Cited by 842 · see citing works
α-Synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy
Wakabayashi, K., Yoshimoto, M., Tsuji, S., & Takahashi, H. (1998) · Neuroscience Letters · doi:10.1016/s0304-3940(98)00407-8 · Cited by 643 · see citing works
McKeith, I. G. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9s347 · Cited by 625 · see citing works
Mollenhauer, B., Locascio, J. J., Schulz‐Schaeffer, W., Sixel‐Döring, F., Trenkwalder, C., & Schlossmacher, M. G. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70014-x · Cited by 623 · 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
The 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
Tokuda, T., Salem, S. A., Allsop, D., Mizuno, T., Nakagawa, M., Qureshi, M. M., Locascio, J. J., Schlossmacher, M. G., & El-Agnaf, O. M. A. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.08.024 · Cited by 425 · see citing works
Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression
Shi, M. Y., Bradner, J. M., Hancock, A. M., Chung, K. A., Quinn, J. F., Peskind, E. R., Galasko, D., Jankovic, J. J., Zabetian, C. P., Kim, H. M., et al. (2010) · Annals of Neurology · doi:10.1002/ana.22311 · Cited by 418 · see citing works
Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders.
Takeda, A., Mallory, M. E., Sundsmo, M. P., Honer, W. G., Hansen, L. A., & Masliah, E. (1998) · Europe PMC (PubMed Central) · Cited by 404 · see citing works
Mollenhauer, B., Cullen, V., Kahn, I., Krastins, B., Outeiro, T. F., Pepivani, I., Ng, J., Schulz-Schaeffer, W., Kretzschmar, H. A., McLean, P. J., et al. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.06.004 · Cited by 382 · see citing works
Jensen, P. H., Hager, H., Nielsen, M. S., Højrup, P., Gliemann, J., & Jakes, R. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.36.25481 · Cited by 377 · see citing works
Proposed neuropathological criteria for the <i>post mortem</i> diagnosis of multiple system atrophy
Trojanowski, J. Q., Revesz, T., & the Neuropathology Working Group on MSA (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00907.x · Cited by 349 · see citing works
The role of alpha-synuclein in neurotransmission and synaptic plasticity
Cheng, F., Vivacqua, G., & Yu, S. (2010) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2010.12.001 · Cited by 238 · see citing works
Multiple-system atrophy: a new α-synuclein disease?
Gai, W., Power, J., Blumbergs, P. C., & Blessing, W. W. (1998) · The Lancet · doi:10.1016/s0140-6736(05)79256-4 · Cited by 229 · see citing works
A Novel Protease Homolog Differentially Expressed in Breast and Ovarian Cancer
Anisowicz, A., Sotiropoulou, G., Stenman, G., Mok, S. C., & Sager, R. (1996) · Molecular Medicine · doi:10.1007/bf03401646 · Cited by 214 · 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
Waxman, E. A., & Giasson, B. I. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0297-11.2011 · Cited by 193 · 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
Yamashiro, K., Tsuruoka, N., Kodama, S., et al. (1997) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(96)00187-x · Cited by 170 · see citing works
Zyme, a Novel and Potentially Amyloidogenic Enzyme cDNA Isolated from Alzheimer's Disease Brain
Little, S. P., Dixon, E. P., Norris, F. A., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.40.25135 · Cited by 164 · see citing works
Magklara, A., Mellati, A. A., Wasney, G. A., et al. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01271-3 · Cited by 157 · see citing works
Kasuga, 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
McKeith, I. G., Burn, D. J., Ballard, C. G., Collerton, D., Jaros, E., Morris, C. M., McLaren, A., Perry, E. K., Perry, R., Piggott, M. A., et al. (2003) · Seminars in Clinical Neuropsychiatry · doi:10.1053/scnp.2003.50006 · Cited by 134 · see citing works
Diamandis, E. P., Yousef, G. M., Soosaipillai, A. R., et al. (2000) · Clinical Biochemistry · doi:10.1016/s0009-9120(00)00145-4 · Cited by 124 · see citing works
Tateno, F., Sakakibara, R., Kawai, T., Kishi, M., & Murano, T. (2012) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0b013e31823899cc · Cited by 121 · see citing works
Human Kallikrein 6 as a Biomarker of Alzheimer’s Disease
Diamandis, E. P., Yousef, G. M., Petraki, C. D., et al. (2000) · Clinical Biochemistry · doi:10.1016/s0009-9120(00)00185-5 · Cited by 118 · see citing works
Mollenhauer, B., El‐Agnaf, O. M. A., Marcus, K., Trenkwalder, C., & Schlossmacher, M. G. (2010) · Biomarkers in Medicine · doi:10.2217/bmm.10.90 · Cited by 114 · see citing works
Ogawa, K., Yamada, T., Tsujioka, Y., et al. (2000) · Psychiatry and Clinical Neurosciences · doi:10.1046/j.1440-1819.2000.00731.x · Cited by 113 · see citing works
Controlling the mass action of α‐synuclein in Parkinson’s disease
Kim, C., & Lee, S. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05612.x · Cited by 105 · see citing works
Altered CSF Orexin and α-Synuclein Levels in Dementia Patients
Wennström, M., Londos, E., Minthon, L., & Nielsen, H. M. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-111655 · Cited by 104 · see citing works
Self-citationSubstrate Specificity of Human Kallikrein 6
Ângelo, P. F., Lima, A. R., Alves, F. M., Blaber, S. I., Scarisbrick, I. A., Blaber, M., Juliano, L., & Juliano, M. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m510096200 · Cited by 100 · see citing works
Cerebrospinal Fluid α-Synuclein Does Not Discriminate Between Dementia Disorders
Spies, P. E., Melis, R. J. F., Sjögren, M. J. C., Rikkert, M. G. M. O., & Verbeek, M. M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-0955 · Cited by 93 · 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
Stimulatory effect of <b>α</b>‐synuclein on the tau‐phosphorylation by GSK‐3<b>β</b>
Kawakami, F., Suzuki, M., Shimada, N., Kagiya, G., Ohta, E., Tamura, K., Maruyama, H., & Ichikawa, T. (2011) · The FEBS Journal · doi:10.1111/j.1742-4658.2011.08389.x · Cited by 82 · see citing works
The physiology and pathobiology of human kallikrein-related peptidase 6 (KLK6)
Bayani, J., & Diamandis, E. P. (2011) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm.2011.750 · Cited by 78 · see citing works
Extracellular neurosin degrades α-synuclein in cultured cells
Tatebe, H., Watanabe, Y., Kasai, T., Mizuno, T., Nakagawa, M., Tanaka, M., & Tokuda, T. (2010) · Neuroscience Research · doi:10.1016/j.neures.2010.04.008 · Cited by 76 · see citing works
Cleavage of normal and pathological forms of α-synuclein by neurosin in vitro
Kasai, T., Tokuda, T., Yamaguchi, N., Watanabe, Y., Kametani, F., Nakagawa, M., & Mizuno, T. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.02.057 · Cited by 76 · see citing works
Mitsui, S., Okui, A., Uemura, H., et al. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04818.x · Cited by 53 · see citing works
Kallikrein-related peptidase 6 in Alzheimer's disease and vascular dementia
Ashby, E. L., Kehoe, P. G., & Love, S. (2010) · Brain Research · doi:10.1016/j.brainres.2010.09.017 · Cited by 51 · see citing works
Cerebrospinal Fluid Biomarkers for Dementia with Lewy Bodies
Mukaetova‐Ladinska, E. B., Monteith, R., & Perry, E. K. (2010) · International Journal of Alzheimer s Disease · doi:10.4061/2010/536538 · Cited by 37 · see citing works
Cloning and characterization of novel isoforms of the human kallikrein 6 gene
Pampalakis, G., Kurlender, L., Diamandis, E. P., et al. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.04.205 · Cited by 37 · see citing works
Okui, A., Kominami, K., Uemura, H., et al. (2001) · Neuroreport · doi:10.1097/00001756-200105250-00011 · Cited by 32 · see citing works
Value of Measuring Plasmatic Levels of Neurosin in the Diagnosis of Alzheimer's Disease
Menéndez‐González, M., Castro, P. G., Suárez, A., et al. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14106 · Cited by 24 · see citing works
Nielsen, H. M., Wennström, M., Hansson, O., et al. (2010) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.05.1219 · Cited by 1 · see citing works
Self-citationNielsen, H. M., Wennström, M., Hansson, O., et al. (2010) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.08.004 · Cited by 1 · see citing works
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- Authors
- Wennström, M., Surova, Y., Hall, S., Nilsson, C., Minthon, L., Boström, F., Hansson, O., & Nielsen, H. M.
- Affiliations
- Lund University (SE)
- Mayo Clinic (US)
- Corresponding author
- Nielsen, Henrietta M.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-01-08
- Volume
- 8
- Issue
- 1
- Pages
- e53250
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3540093
- OpenAlex
- W1975699199
- Cited by
- 141
- References
- 61
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 4 · 2023: 10 · 2022: 11 · 2021: 8 · 2020: 12 · 2019: 7 · 2018: 12 · 2017: 7 · 2016: 13 · 2015: 19 · 2014: 18 · 2013: 8
- FWCI
- 12.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Funders
- Lunds Universitet
- Vetenskapsrådet
- Swedish Brain Power
- Svenska Läkaresällskapet
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- alpha-synuclein, synucleinopathies, Parkinson's disease, dementia with Lewy bodies, Parkinson's disease dementia, Alzheimer's disease, cerebrospinal fluid biomarkers, phosphorylated tau, Lewy bodies, APOE ε4
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Female, Humans, Kallikreins, Male, Middle Aged, Parkinson Disease, Biomarkers, Lewy Body Disease, alpha-Synuclein
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