16
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Contactin-1 Is Reduced in Cerebrospinal Fluid of Parkinson’s Disease Patients and Is Present within Lewy Bodies

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Synaptic degeneration is an early phenomenon in Parkinson’s disease (PD) pathogenesis. We aimed to investigate whether levels of synaptic proteins contactin-1 and contactin-2 in cerebrospinal fluid (CSF) of PD patients are reduced compared to dementia with Lewy bodies (DLB) patients and controls and to evaluate their relationship with α-synuclein aggregation. Contactin-1 and -2 were measured in CSF from PD patients ( n = 58), DLB patients ( n = 72) and age-matched controls ( n = 90). Contactin concentration differences between diagnostic groups were assessed by general linear models adjusted for age and sex. Contactin immunoreactivity was characterized in postmortem substantia nigra, hippocampus and entorhinal cortex tissue of PD patients ( n = 4) and controls ( n = 4), and its relation to α-syn aggregation was evaluated using confocal laser scanning microscopy. Contactin-1 levels were lower in PD patients (42 (36–49) pg/mL) compared to controls (52 (44–58) pg/mL, p = 0.003) and DLB patients (56 (46–67) pg/mL, p = 0.001). Contactin-2 levels were similar across all diagnostic groups. Within the PD patient group, contactin-1 correlated with t-α-syn, tTau and pTau ( r = 0.30–0.50, p < 0.05), whereas contactin-2 only correlated with t-α-syn ( r = 0.34, p = 0.03). Contactin-1 and -2 were observed within nigral and cortical Lewy bodies and clustered within bulgy Lewy neurites in PD brains. A decrease in CSF contactin-1 may reflect synaptic degeneration underlying Lewy body pathology in PD.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          alpha-Synuclein is phosphorylated in synucleinopathy lesions.

          The deposition of the abundant presynaptic brain protein alpha-synuclein as fibrillary aggregates in neurons or glial cells is a hallmark lesion in a subset of neurodegenerative disorders. These disorders include Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy, collectively referred to as synucleinopathies. Importantly, the identification of missense mutations in the alpha-synuclein gene in some pedigrees of familial PD has strongly implicated alpha-synuclein in the pathogenesis of PD and other synucleinopathies. However, specific post-translational modifications that underlie the aggregation of alpha-synuclein in affected brains have not, as yet, been identified. Here, we show by mass spectrometry analysis and studies with an antibody that specifically recognizes phospho-Ser 129 of alpha-synuclein, that this residue is selectively and extensively phosphorylated in synucleinopathy lesions. Furthermore, phosphorylation of alpha-synuclein at Ser 129 promoted fibril formation in vitro. These results highlight the importance of phosphorylation of filamentous proteins in the pathogenesis of neurodegenerative disorders.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            The Emerging Evidence of the Parkinson Pandemic

            Neurological disorders are now the leading source of disability globally, and the fastest growing neurological disorder in the world is Parkinson disease. From 1990 to 2015, the number of people with Parkinson disease doubled to over 6 million. Driven principally by aging, this number is projected to double again to over 12 million by 2040. Additional factors, including increasing longevity, declining smoking rates, and increasing industrialization, could raise the burden to over 17 million. For most of human history, Parkinson has been a rare disorder. However, demography and the by-products of industrialization have now created a Parkinson pandemic that will require heightened activism, focused planning, and novel approaches.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort. The Parkinson Study Group.

              The DATATOP database, which includes clinical information on 800 patients with early untreated Parkinson's disease (PD), is well suited to explore clinical heterogeneity in PD. Patients with early-onset PD (less than or equal to 40 years, N = 33) reached the same level of disability as the late-onset PD (greater than or equal to 70 years, N = 85) group at a significantly slower rate (2.9 vs. 1.7 years). Early-onset PD patients functioned cognitively better than late-onset PD patients. Bradykinesia, and postural instability and gait difficulty (PIGD), were more common at onset in patients with a rapid rate of disease progression ("malignant PD"; duration of symptoms less than 1 year and Hoehn/Yahr stage of 2.5, N = 11) as compared with those with a relatively slow rate of progression ("benign PD"; duration of symptoms greater than 4 years, N = 65). Comparisons of tremor-dominant PD (mean tremor score/mean PIGD score less than or equal to 1.5, N = 441) with the PIGD-dominant type (mean tremor score/mean PIGD score greater than or equal to 1.0, N = 233) provided support for the existence of clinical subtypes. The PIGD group reported significantly greater subjective intellectual, motor, and occupational impairment than the tremor group. Stage II patients had higher depression scores than stage I patients. Among the patients participating in the DATATOP, older age at onset with bradykinesia, or with the PIGD form of PD, is associated with more functional disability than when the symptoms are dominated by tremor or begin at a younger age.
                Bookmark

                Author and article information

                Journal
                Biomolecules
                Biomolecules
                biomolecules
                Biomolecules
                MDPI
                2218-273X
                12 August 2020
                August 2020
                : 10
                : 8
                : 1177
                Affiliations
                [1 ]Neurochemistry Laboratory, Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, 1105 AZ Amsterdam, The Netherlands; madhurima.cob@ 123456gmail.com (M.C.); m.delcampomilan@ 123456amsterdamumc.nl (M.D.C.)
                [2 ]Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, 1105 AZ Amsterdam, The Netherlands; i.vansteenoven@ 123456amsterdamumc.nl (I.v.S.); wm.vdflier@ 123456amsterdamumc.nl (W.M.v.d.F.); a.lemstra@ 123456amsterdamumc.nl (A.W.L.)
                [3 ]Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, 1105 AZ Amsterdam, The Netherlands; e.timmermans@ 123456amsterdamumc.nl (E.H.); l.oosterveld@ 123456amsterdamumc.nl (L.O.); wdj.vandeberg@ 123456amsterdamumc.nl (W.D.J.v.d.B.)
                [4 ]Department of Neurology, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, 1105 AZ Amsterdam, The Netherlands; h.berendse@ 123456amsterdamumc.nl
                [5 ]Department of Epidemiology & Biostatistics, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, 1105 AZ Amsterdam, The Netherlands
                Author notes
                [* ]Correspondence: c.teunissen@ 123456amsterdamumc.nl ; Tel.: +31-20-4443-680
                Author information
                https://orcid.org/0000-0003-1647-3307
                https://orcid.org/0000-0003-2808-3699
                https://orcid.org/0000-0002-6175-5357
                Article
                biomolecules-10-01177
                10.3390/biom10081177
                7463939
                32806791
                25496623-af0e-4126-840a-b7417df067e2
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 13 June 2020
                : 05 August 2020
                Categories
                Article

                contactin,lewy bodies,cerebrospinal fluid (csf),biomarker,synaptic degeneration,parkinson’s disease (pd),dementia with lewy bodies (dlb)

                Comments

                Comment on this article