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      α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson’s disease

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          Abstract

          A diagnosis of motor Parkinson’s disease (PD) is preceded by a prolonged premotor phase with accumulating neuronal damage. Here we examined the temporal relation between α-synuclein (α-syn) T cell reactivity and PD. A longitudinal case study revealed that elevated α-syn-specific T cell responses were detected prior to the diagnosis of motor PD, and declined after. The relationship between T cell reactivity and early PD in two independent cohorts showed that α-syn-specific T cell responses were highest shortly after diagnosis of motor PD and then decreased. Additional analysis revealed significant association of α-syn-specific T cell responses with age and lower levodopa equivalent dose. These results confirm the presence of α-syn-reactive T cells in PD and show that they are most abundant immediately after diagnosis of motor PD. These cells may be present years before the diagnosis of motor PD, suggesting avenues of investigation into PD pathogenesis and potential early diagnosis.

          Abstract

          α-Synuclein-specific T cell reactivity is preferentially associated with Parkinson’s disease (PD) patients, but the temporal relation with diagnosis was previously unknown. This study reveals that α-syn-reactive T cells are highest before and shortly after diagnosis of motor PD, and then decrease.

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          Most cited references37

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          The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

          To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. Validation study. A community clinic and an academic center. Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
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            The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

            The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. Copyright © 2011. Published by Elsevier Inc.
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              Clinical diagnosis of Alzheimer's disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease

              Neurology, 34(7), 939-939
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                Author and article information

                Contributors
                ds43@cumc.columbia.edu
                alex@lji.org
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                20 April 2020
                20 April 2020
                2020
                : 11
                : 1875
                Affiliations
                [1 ]Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037 USA
                [2 ]ISNI 0000 0001 2285 2675, GRID grid.239585.0, Department of Neurology, , Columbia University Medical Center, ; Columbia, NY 10032 USA
                [3 ]ISNI 0000 0001 2264 7217, GRID grid.152326.1, Vanderbilt University School of Medicine, ; Nashville, TN 37235 USA
                [4 ]ISNI 0000 0004 0436 6763, GRID grid.1025.6, Institute for Immunology and Infectious Diseases, , Murdoch University, ; Perth, WA 6150 Australia
                [5 ]ISNI 0000 0001 2164 9667, GRID grid.419681.3, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, ; Bethesda, MD 20892 USA
                [6 ]ISNI 0000000106344187, GRID grid.265892.2, Department of Neurology, , University of Alabama at Birmingham, ; Birmingham, AL 35233 USA
                [7 ]ISNI 0000 0001 2299 3507, GRID grid.16753.36, Shirley Ryan AbilityLab, Northwestern University Feinberg School of Medicine, ; Chicago, IL 60611 USA
                [8 ]ISNI 0000 0001 2107 4242, GRID grid.266100.3, Department of Neurology, , University of California San Diego, ; La Jolla, CA 92093 USA
                [9 ]ISNI 0000 0001 2107 4242, GRID grid.266100.3, Department of Medicine, , University of California San Diego, ; La Jolla, CA 92093 USA
                [10 ]ISNI 0000000419368729, GRID grid.21729.3f, Department of Neurology, , Columbia University, ; New York, NY 10032 USA
                [11 ]ISNI 0000000419368729, GRID grid.21729.3f, Departments of Psychiatry and Pharmacology, , Columbia University, ; New York, NY 10032 USA
                [12 ]ISNI 0000 0000 8499 1112, GRID grid.413734.6, New York State Psychiatric Institute, ; New York, NY 10032 USA
                Author information
                http://orcid.org/0000-0001-7302-8002
                http://orcid.org/0000-0002-7623-3383
                http://orcid.org/0000-0003-0762-9656
                Article
                15626
                10.1038/s41467-020-15626-w
                7171193
                32313102
                16ee7302-5be6-4efe-adf3-fb431093e0ee
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 14 October 2019
                : 20 March 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000065, U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS);
                Award ID: R01NS095435
                Award ID: P50NS108675
                Award Recipient :
                Funded by: U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
                Funded by: FundRef https://doi.org/10.13039/100000049, U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging);
                Award ID: P50AG08702
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100013301, Parkinson's Foundation (Parkinson's Foundation, Inc.);
                Funded by: FundRef https://doi.org/10.13039/100000864, Michael J. Fox Foundation for Parkinson's Research (Michael J. Fox Foundation);
                Funded by: UCSD-LJI Program in Immunology
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                autoimmunity,parkinson's disease
                Uncategorized
                autoimmunity, parkinson's disease

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