Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013;8(1):e53250.
doi: 10.1371/journal.pone.0053250. Epub 2013 Jan 8.

Low CSF Levels of Both α-Synuclein and the α-Synuclein Cleaving Enzyme Neurosin in Patients With Synucleinopathy

Affiliations
Free PMC article

Low CSF Levels of Both α-Synuclein and the α-Synuclein Cleaving Enzyme Neurosin in Patients With Synucleinopathy

Malin Wennström et al. PLoS One. .
Free PMC article

Abstract

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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Specificity of the biotinylated goat anti-human neurosin antibody used in the neurosin ELISA was evaluated by western blotting (A).
Lane 1 recombinant human neurosin, lane 2 immunoprecipitated neurosin from pooled human CSF. CSF concentrations of neurosin (B) and α-synuclein (C). Significant differences are indicated by p-values generated by use of ANCOVA group comparisons with correction for age or ANOVA followed by Bonferroni posthoc testing.
Figure 2
Figure 2. CSF levels of neurosin (A) and α-synuclein (B) in non-demented controls (CON), Alzheimer's disease patients (AD) and patients with Parkinson's disease, Parkinson's disease dementia and dementia with Lewy bodies grouped into one cumulative group of patients with synucleinopathy (SYN).
Significant differences in CSF markers, as indicated by the p-values, were evaluated using ANCOVA group comparisons with correction for age or ANOVA followed by Bonferroni posthoc testing.

Similar articles

See all similar articles

Cited by 40 articles

See all "Cited by" articles

References

    1. Mollenhauer B, El-Agnaf OM, Marcus K, Trenkwalder C, Schlossmacher MG (2010) Quantification of alpha-synuclein in cerebrospinal fluid as a biomarker candidate: review of the literature and considerations for future studies. Biomark Med 4: 683–699. - PubMed
    1. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, et al. (1997) Alpha-synuclein in Lewy bodies. Nature 388: 839–840. - PubMed
    1. Takeda A, Mallory M, Sundsmo M, Honer W, Hansen L, et al. (1998) Abnormal accumulation of NACP/alpha-synuclein in neurodegenerative disorders. Am J Pathol 152: 367–372. - PMC - PubMed
    1. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, et al. (2003) Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 24: 197–211. - PubMed
    1. McKeith IG (2006) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. J Alzheimers Dis 9: 417–423. - PubMed

Publication types

Grant support

The Swedish Dementia Foundation (H.M.N.), the Swedish Alzheimer Foundation (H.M.N., O.H.), the Swedish Research Council (O.H.), Gamla tjänarinnor (H.M.N., O.H.), Torsten and Ragnar Söderberg Foundation (O.H.), the Swedish Society of Medicine (O.H.), the regional agreement on medical training and clinical research (A.L.F.) between the Skåne County Council and Lund University (L.M., M.W., H.M.N., O.H.) and Swedish Brain Power (L.M.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Feedback