Absence of elevated anti–α-synuclein and anti-EBV latent membrane protein antibodies in PD

Woulfe, John; Duke, Richard C.; Middeldorp, Jaap M.; Stevens, Servi J. C.; Vervoort, M. B. H. J.; Hashimoto, M.; Masliah, E.; Chan, P. L.; Monte, Donato A. Di; Langston, J. W.; Petzinger, Giselle M.; Hoogendoorn, Hugh; Muñoz, David G.

doi:10.1212/wnl.58.9.1435

Cited by 29 publications

(35 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, we adopt the RP-HPLC step of Snca purification for all the studies reported here. The results we have obtained on the prevalence of anti-Snca antibodies in our case (iPD) and control (healthy subjects) study are in agreement with those published previously (Woulfe et al, 2002; Papachroni et al, 2007; Smith et al, 2012; Besong-Agbo et al, 2013) showing that there is no significant difference in the prevalence of anti-Snca antibodies between iPD patients and healthy controls. Furthermore, neither there is a higher prevalence of anti-Snca antibodies in non-manifesting (Asymp) or manifesting (Symp) LRRK2 carriers than in iPD patients or healthy controls when cut-off for anti-Snca positive reaction was established at OD ≥ 0.3 by endpoint ELISA and titer by immunoblot ≥1/100.…”

Section: Discussionsupporting

confidence: 93%

“…The initial study of the presence of antibodies against Snca in human subjects was undertaken because commercially available anti-latent protein 1 EBV antibodies cross-reacted with Snca (Woulfe et al, 2000) and later the same authors reported no difference in prevalence of anti-Snca reactivity between idiopathic PD (iPD) patients and healthy controls (Woulfe et al, 2002). Afterwards, multi-epitopic Snca antibodies were found in patients from families with uncharacterized familial forms of PD, but its frequency was not significantly higher in iPD patients with respect to healthy controls (Papachroni et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Epitope Mapping of Antibodies to Alpha-Synuclein in LRRK2 Mutation Carriers, Idiopathic Parkinson Disease Patients, and Healthy Controls

Álvarez-Castelao

Gorostidi

Ruíz‐Martínez

et al. 2014

Front. Aging Neurosci.

View full text Add to dashboard Cite

Alpha-synuclein (Snca) plays a major role in Parkinson disease (PD). Circulating anti-Snca antibodies has been described in PD patients and healthy controls, but they have been poorly characterized. This study was designed to assess the prevalence of anti-Snca reactivity in human subjects carrying the LRRK2 mutation, idiopathic PD (iPD) patients, and healthy controls and to map the epitopes of the anti-Snca antibodies. Antibodies to Snca were detected by ELISA and immunoblotting using purified recombinant Snca in plasma from individuals carrying LRRK2 mutations (104), iPD patients (59), and healthy controls (83). Epitopes of antibodies were mapped using recombinant protein constructs comprising different regions of Snca. Clear positive anti-Snca reactivity showed no correlation with age, sex, years of evolution, or the disability scores for PD patients and anti-Snca reactivity was not prevalent in human patients with other neurological or autoimmune diseases. Thirteen of the positive individuals were carriers of LRRK2 mutations either non-manifesting (8 out 49 screened) or manifesting (5 positive out 55), three positive (out of 59) were iPD patients, and five positive (out of 83) were healthy controls. Epitope mapping showed that antibodies against the N-terminal (a.a. 1–60) or C-terminal (a.a. 109–140) regions of Snca predominate in LRRK2 mutation carriers and iPD patients, being N122 a critical amino acid for recognition by the anti-C-terminal directed antibodies. Anti-Snca circulating antibodies seem to cluster within families carrying the LRRK2 mutation indicating possible genetic or common environmental factors in the generation of anti-Snca antibodies. These results suggest that case-controls’ studies are insufficient and further studies in family cohorts of patients and healthy controls should be undertaken, to progress in the understanding of the possible relationship of anti-Snca antibodies and PD pathology.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Epitope Mapping of Antibodies to Alpha-Synuclein in LRRK2 Mutation Carriers, Idiopathic Parkinson Disease Patients, and Healthy Controls

Álvarez-Castelao

Gorostidi

Ruíz‐Martínez

et al. 2014

Front. Aging Neurosci.

View full text Add to dashboard Cite

show abstract

“…Although early studies failed to detect the native form of α-synuclein in the CSF of PD and control patients (Jakowec et al, 1998), later studies have detected monomeric SNC in the CSF, with similar levels in PD patients and controls (Borghi et al, 2000). Several studies have found similar CSF total α-synuclein levels in PD patients and in controls (Woulfe et al, 2002; Ohrfelt et al, 2009; Park et al, 2011; Parnetti et al, 2011; Tateno et al, 2012) and others decreased CSF α-synuclein in PD (Tokuda et al, 2006; Hong et al, 2010; Mollenhauer et al, 2011, 2013; Hall et al, 2012; Wang et al, 2012; Kang et al, 2013; Wennström et al, 2013; Parnetti et al, 2014a,b; Mondello et al, 2014; van Dijk et al, 2014), DLBD (Parnetti et al, 2011; Wennström et al, 2013), MSA (Wang et al, 2012; Mondello et al, 2014), and PSP (Wang et al, 2012). Four studies have reported increased CSF oligomeric α-synuclein levels in PD compared with controls (Tokuda et al, 2010; Park et al, 2011; Parnetti et al, 2014a,b), and one of them showed increased CSF α-Syn in PD patients compared with patients with PSP and AD (Tokuda et al, 2010).…”

Section: Proteins Involved In the Pathogenesis Of Parkinson's Diseasementioning

confidence: 81%

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

Jiménez‐Jiménez¹,

Alonso‐Navarro

García‐Martín

et al. 2014

Front. Cell. Neurosci.

View full text Add to dashboard Cite

The blood-brain barrier supplies brain tissues with nutrients and filters certain compounds from the brain back to the bloodstream. In several neurodegenerative diseases, including Parkinson's disease (PD), there are disruptions of the blood-brain barrier. Cerebrospinal fluid (CSF) has been widely investigated in PD and in other parkinsonian syndromes with the aim of establishing useful biomarkers for an accurate differential diagnosis among these syndromes. This review article summarizes the studies reported on CSF levels of many potential biomarkers of PD. The most consistent findings are: (a) the possible role of CSF urate on the progression of the disease; (b) the possible relations of CSF total tau and phosphotau protein with the progression of PD and with the preservation of cognitive function in PD patients; (c) the possible value of CSF beta-amyloid 1-42 as a useful marker of further cognitive decline in PD patients, and (d) the potential usefulness of CSF neurofilament (NFL) protein levels in the differential diagnosis between PD and other parkinsonian syndromes. Future multicentric, longitudinal, prospective studies with long-term follow-up and neuropathological confirmation would be useful in establishing appropriate biomarkers for PD.

show abstract

“…It has been shown that antibodies against EBV could cross-react with asynuclein in human brain [33]. A small study found that PD patients had neither increased serum antibodies against EB virus nor asynuclein [34]. However, a large epidemiological study provides evidence that EBV seropositivity in patients with PD is significantly higher than that in the general population [24].…”

Section: Discussionmentioning

confidence: 99%

The association between infectious burden and Parkinson's disease: A case-control study

Bu¹,

Wang²,

Xiang³

et al. 2015

Parkinsonism & Related Disorders

135

123

View full text Add to dashboard Cite

Absence of elevated anti–α-synuclein and anti-EBV latent membrane protein antibodies in PD

Cited by 29 publications

References 12 publications

Epitope Mapping of Antibodies to Alpha-Synuclein in LRRK2 Mutation Carriers, Idiopathic Parkinson Disease Patients, and Healthy Controls

Epitope Mapping of Antibodies to Alpha-Synuclein in LRRK2 Mutation Carriers, Idiopathic Parkinson Disease Patients, and Healthy Controls

Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

The association between infectious burden and Parkinson's disease: A case-control study

Contact Info

Product

Resources

About