{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:30:45Z","timestamp":1791898245240,"version":"4.3.4"},"reference-count":92,"publisher":"SAGE Publications","issue":"s1","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPD"],"published-print":{"date-parts":[[2022,9,27]]},"abstract":"<jats:p>Ageing is a major risk factor for most neurodegenerative diseases, including Parkinson\u2019s disease (PD). Progressive age-related dysregulation of the immune system is termed immunosenescence and is responsible for the weakened response to novel antigens, increased susceptibility to infections and reduced effectiveness of vaccines seen in the elderly. Immune activation, both within the brain and periphery, is heavily implicated in PD but the role of immunosenescence has not been fully explored. Studies to date provide some evidence for an attenuation in immunosenescence in PD, particularly a reduction in senescent CD8 T lymphocytes in PD cases compared to similarly aged controls. Here, we discuss recent evidence of age-related immune abnormalities in PD with a focus on T cell senescence and explore their potential role in disease pathogenesis and development.<\/jats:p>","DOI":"10.3233\/jpd-223228","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T11:34:44Z","timestamp":1654256084000},"page":"S93-S104","source":"Crossref","is-referenced-by-count":15,"title":["Age-Related Adaptive Immune Changes in Parkinson\u2019s Disease"],"prefix":"10.1177","volume":"12","author":[{"given":"Antonina","family":"Kouli","sequence":"first","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, John Van Geest Centre for Brain Repair, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline H.","family":"Williams-Gray","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences, University of Cambridge, John Van Geest Centre for Brain Repair, Cambridge, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JPD-223228_ref1","doi-asserted-by":"crossref","first-page":"e7156435","DOI":"10.1155\/2018\/7156435","article-title":"Aging-induced biological changes and cardiovascular diseases","volume":"2018","author":"Fajemiroye","year":"2018","journal-title":"Biomed Res Int"},{"key":"10.3233\/JPD-223228_ref2","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/s41416-019-0721-1","article-title":"Cancer as a disease of old age: Changing mutational and microenvironmental landscapes","volume":"122","author":"Laconi","year":"2020","journal-title":"Br J Cancer"},{"key":"10.3233\/JPD-223228_ref3","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a risk factor for neurodegenerative disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat Rev Neurol"},{"key":"10.3233\/JPD-223228_ref4","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1016\/j.vaccine.2005.08.105","article-title":"Antibody response to influenza vaccination in the elderly: A quantitative review","volume":"24","author":"Goodwin","year":"2006","journal-title":"Vaccine"},{"key":"10.3233\/JPD-223228_ref5","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1007\/s00018-012-0970-0","article-title":"Immune aging and autoimmunity","volume":"69","author":"Goronzy","year":"2012","journal-title":"Cell Mol Life Sci"},{"key":"10.3233\/JPD-223228_ref6","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/mds.26563","article-title":"Serum immune markers and disease progression in an incident Parkinson\u2019s disease cohort (ICICLE-PD)","volume":"31","author":"Williams-Gray","year":"2016","journal-title":"Mov Disord"},{"key":"10.3233\/JPD-223228_ref7","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.bbi.2020.01.018","article-title":"Peripheral innate immune and bacterial signals relate to clinical heterogeneity in Parkinson\u2019s disease","volume":"87","author":"Wijeyekoon","year":"2020","journal-title":"Brain Behav Immun"},{"key":"10.3233\/JPD-223228_ref8","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1007\/s11481-012-9402-z","article-title":"CD4+regulatory and effector\/memory T cell subsets profile motor dysfunction in Parkinson\u2019s disease","volume":"7","author":"Saunders","year":"2012","journal-title":"J Neuroimmune Pharmacol"},{"key":"10.3233\/JPD-223228_ref10","doi-asserted-by":"crossref","first-page":"3460","DOI":"10.3389\/fimmu.2020.604591","article-title":"Immunosenescence study of T cells: A systematic review","volume":"11","author":"Rodriguez","year":"2021","journal-title":"Front Immunol"},{"key":"10.3233\/JPD-223228_ref11","first-page":"1680","article-title":"T cell replicative senescence in human aging","volume":"19","author":"Chou","year":"2013","journal-title":"Curr Pharm Des"},{"key":"10.3233\/JPD-223228_ref12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/cyto.a.22351","article-title":"From \u201ctruly na\u00efve\u201d to \u201cexhaustedsenescent\u201d T cells: When markers predict functionality","volume":"85","author":"Larbi","year":"2014","journal-title":"Cytometry A"},{"key":"10.3233\/JPD-223228_ref13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1189\/jlb.0809566","article-title":"CD57+T lymphocytes and functional immune deficiency","volume":"87","author":"Focosi","year":"2010","journal-title":"J Leukoc Biol"},{"key":"10.3233\/JPD-223228_ref14","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1182\/blood-2002-07-2103","article-title":"Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+T cells","volume":"101","author":"Brenchley","year":"2003","journal-title":"Blood"},{"key":"10.3233\/JPD-223228_ref15","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/0531-5565(94)90073-6","article-title":"Decline in CD28+T cells in centenarians and in long-term T cell cultures: A possible cause for both in vivo and in vitro immunosenescence","volume":"29","author":"Effros","year":"1994","journal-title":"Exp Gerontol"},{"key":"10.3233\/JPD-223228_ref16","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.it.2016.09.002","article-title":"Senescence of T lymphocytes: Implications for enhancing human immunity","volume":"37","author":"Akbar","year":"2016","journal-title":"Trends Immunol"},{"key":"10.3233\/JPD-223228_ref17","doi-asserted-by":"crossref","first-page":"4260","DOI":"10.1182\/blood-2002-11-3577","article-title":"Proliferation and differentiation potential of human CD8+memory T-cell subsets in response to antigen or homeostatic cytokines","volume":"101","author":"Geginat","year":"2003","journal-title":"Blood"},{"key":"10.3233\/JPD-223228_ref18","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.3390\/ijms18081742","article-title":"Markers of T cell senescence in humans","volume":"18","author":"Xu","year":"2017","journal-title":"Int J Mol Sci"},{"key":"10.3233\/JPD-223228_ref19","doi-asserted-by":"crossref","first-page":"26892","DOI":"10.1038\/srep26892","article-title":"Differential effects of Cytomegalovirus carriage on the immune phenotype of middle-aged males and females","volume":"6","author":"van der Heiden","year":"2016","journal-title":"Sci Rep"},{"key":"10.3233\/JPD-223228_ref20","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1099\/vir.0.036004-0","article-title":"Infection with cytomegalovirus but not herpes simplex virus induces the accumulation of late-differentiated CD4+and CD8+T-cells in humans","volume":"92","author":"Derhovanessian","year":"2011","journal-title":"J Gen Virol"},{"key":"10.3233\/JPD-223228_ref21","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.4049\/jimmunol.169.4.1984","article-title":"Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals","volume":"169","author":"Khan","year":"2002","journal-title":"J Immunol"},{"key":"10.3233\/JPD-223228_ref22","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.4049\/jimmunol.176.4.2645","article-title":"Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly","volume":"176","author":"Hadrup","year":"2006","journal-title":"J Immunol"},{"key":"10.3233\/JPD-223228_ref23","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1399-0039.2007.00891.x","article-title":"Immunosenescence: Deficits in adaptive immunity in the elderly","volume":"70","author":"Hakim","year":"2007","journal-title":"Tissue Antigens"},{"key":"10.3233\/JPD-223228_ref24","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fimmu.2013.00316","article-title":"The effect of age on thymic function","volume":"4","author":"Palmer","year":"2013","journal-title":"Front Immunol"},{"key":"10.3233\/JPD-223228_ref25","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1080\/10446670310001598465","article-title":"Essential microenvironment for thymopoiesis is preserved in human adult and aged thymus","volume":"10","author":"Shiraishi","year":"2003","journal-title":"Clin Dev Immunol"},{"key":"10.3233\/JPD-223228_ref26","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.it.2009.04.003","article-title":"Thymic involution and immune reconstitution","volume":"30","author":"Lynch","year":"2009","journal-title":"Trends Immunol"},{"key":"10.3233\/JPD-223228_ref27","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1007\/s11357-011-9301-x","article-title":"The association between systemic inflammation and cognitive performance in the elderly: The Sydney Memory and Ageing Study","volume":"34","author":"Trollor","year":"2012","journal-title":"Age"},{"key":"10.3233\/JPD-223228_ref28","doi-asserted-by":"crossref","first-page":"4358","DOI":"10.1038\/s41598-021-83991-7","article-title":"Inflammaging markers characteristic of advanced age show similar levels with frailty and dependency","volume":"11","author":"Alberro","year":"2021","journal-title":"Sci Rep"},{"key":"10.3233\/JPD-223228_ref29","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s12974-018-1206-5","article-title":"Abnormalities of age-related T cell senescence in Parkinson\u2019s disease","volume":"15","author":"Williams-Gray","year":"2018","journal-title":"J Neuroinflammation"},{"key":"10.3233\/JPD-223228_ref30","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1186\/s12974-021-02287-9","article-title":"T lymphocyte senescence is attenuated in Parkinson\u2019s disease","volume":"18","author":"Kouli","year":"2021","journal-title":"J Neuroinflammation"},{"key":"10.3233\/JPD-223228_ref31","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.jgo.2011.08.004","article-title":"p16INK4a: Acentral player in cellular senescence and a promising agingbiomarker in elderly cancer patients","volume":"2","author":"Vandenberk","year":"2011","journal-title":"J\u00a0Geriatr Oncol"},{"key":"10.3233\/JPD-223228_ref32","doi-asserted-by":"crossref","first-page":"13119","DOI":"10.3390\/ijms222313119","article-title":"Reduced immunosenescence of peripheral blood T cells in Parkinson\u2019s disease with CMV infection background","volume":"22","author":"Vavilova","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.3233\/JPD-223228_ref33","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41421-021-00280-3","article-title":"Single-cell transcriptome and TCR profiling reveal activated and expanded T cell populations in Parkinson\u2019s disease","volume":"7","author":"Wang","year":"2021","journal-title":"Cell Discov"},{"key":"10.3233\/JPD-223228_ref34","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3389\/fimmu.2013.00107","article-title":"When aging reaches CD4+T-cells: Phenotypic and functional changes","volume":"4","author":"Moro-Garc\u00eda","year":"2013","journal-title":"Front Immunol"},{"key":"10.3233\/JPD-223228_ref35","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.parkreldis.2005.07.005","article-title":"Alterations of T-lymphocyte populations in Parkinson disease","volume":"11","author":"Baba","year":"2005","journal-title":"Parkinsonism Relat Disord"},{"key":"10.3233\/JPD-223228_ref36","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/S0165-5728(00)00422-7","article-title":"Lymphocyte populations in Parkinson\u2019s disease andin rat models of parkinsonism","volume":"113","author":"Bas","year":"2001","journal-title":"J\u00a0Neuroimmunol"},{"key":"10.3233\/JPD-223228_ref37","doi-asserted-by":"crossref","first-page":"e1125","DOI":"10.1212\/NXI.0000000000001125","article-title":"Abnormal B-cell and Tfh-cell profiles in patients with Parkinson disease: A cross-sectional study","volume":"9","author":"Li","year":"2022","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"10.3233\/JPD-223228_ref38","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.humimm.2009.07.005","article-title":"Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood","volume":"70","author":"Jing","year":"2009","journal-title":"Hum Immunol"},{"key":"10.3233\/JPD-223228_ref39","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.4049\/jimmunol.0901022","article-title":"Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response","volume":"184","author":"Panda","year":"2010","journal-title":"J Immunol"},{"key":"10.3233\/JPD-223228_ref40","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.immuni.2019.08.008","article-title":"Single-cell analysis of human mononuclear phagocytes reveals subset-defining markers and identifies circulating inflammatory dendritic cells.","volume":"51","author":"Dutertre","year":"2019","journal-title":"Immunity"},{"key":"10.3233\/JPD-223228_ref41","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.bbi.2022.01.005","article-title":"Changes in CD163+, CD11b+, and CCR2+peripheral monocytes relate to Parkinson\u2019s disease and cognition","volume":"101","author":"Konstantin Nissen","year":"2022","journal-title":"Brain Behav Immun"},{"key":"10.3233\/JPD-223228_ref42","doi-asserted-by":"crossref","first-page":"e65352","DOI":"10.1371\/journal.pone.0065352","article-title":"Blood dendritic cell frequency declines in idiopathic Parkinson\u2019s disease and is associated with motor symptom severity","volume":"8","author":"Ciaramella","year":"2013","journal-title":"PLoS One"},{"key":"10.3233\/JPD-223228_ref43","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s12974-019-1606-1","article-title":"Regulatory impairment in untreated Parkinson\u2019s disease is not restricted to Tregs: Other regulatory populations are also involved","volume":"16","author":"\u00c1lvarez-Luqu\u00edn","year":"2019","journal-title":"J Neuroinflammation"},{"key":"10.3233\/JPD-223228_ref44","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.exger.2016.12.001","article-title":"Human peripheral late\/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways","volume":"87","author":"Frasca","year":"2017","journal-title":"Exp Gerontol"},{"key":"10.3233\/JPD-223228_ref45","doi-asserted-by":"crossref","first-page":"3587","DOI":"10.4049\/jimmunol.156.10.3587","article-title":"Shortened telomeres in clonally expanded CD28-CD8+T cells imply a replicative history that is distinct from their CD28+CD8+counterparts","volume":"156","author":"Monteiro","year":"1996","journal-title":"J Immunol"},{"key":"10.3233\/JPD-223228_ref46","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/j.0105-2896.2005.00256.x","article-title":"CD28 extinction in human T cells: Altered functions and the program of T-cell senescence","volume":"205","author":"Vallejo","year":"2005","journal-title":"Immunol Rev"},{"key":"10.3233\/JPD-223228_ref47","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S0140-6736(03)12384-7","article-title":"Association between telomere length in blood and mortality in people aged 60 years or older","volume":"361","author":"Cawthon","year":"2003","journal-title":"Lancet"},{"key":"10.3233\/JPD-223228_ref48","doi-asserted-by":"crossref","first-page":"2107.e3","DOI":"10.1016\/j.neurobiolaging.2011.05.022","article-title":"No evidence of substantia nigra telomere shortening in Parkinson\u2019s disease","volume":"32","author":"Hudson","year":"2011","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JPD-223228_ref49","doi-asserted-by":"crossref","first-page":"e113387","DOI":"10.1371\/journal.pone.0113387","article-title":"Long leukocyte telomere length at diagnosis is a risk factor for dementia progression in idiopathic parkinsonism","volume":"9","author":"Degerman","year":"2014","journal-title":"PLoS One"},{"key":"10.3233\/JPD-223228_ref50","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3233\/JPD-191724","article-title":"Senescence and inflammatory markers for predicting clinical progression in Parkinson\u2019s disease: The ICICLE-PD Study","volume":"10","author":"Martin-Ruiz","year":"2020","journal-title":"J Parkinsons Dis"},{"key":"10.3233\/JPD-223228_ref51","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1084\/jem.20080996","article-title":"Human CD4+T cell recent thymic emigrants are identified by protein tyrosine kinase 7 and have reduced immune function","volume":"206","author":"Haines","year":"2009","journal-title":"J Exp Med"},{"key":"10.3233\/JPD-223228_ref52","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1073\/pnas.070061597","article-title":"Identification of a human recent thymic emigrant phenotype","volume":"97","author":"McFarland","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.3233\/JPD-223228_ref53","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1001\/jamaneurol.2016.2742","article-title":"Aberrations in peripheral inflammatory cytokine levels in Parkinson disease: A systematic review and meta-analysis","volume":"73","author":"Qin","year":"2016","journal-title":"JAMA Neurol"},{"key":"10.3233\/JPD-223228_ref54","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1136\/jnnp-2017-317134","article-title":"Peripheral inflammation in prodromal Alzheimer\u2019s and Lewy body dementias","volume":"89","author":"King","year":"2018","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.3233\/JPD-223228_ref55","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1093\/brain\/awz030","article-title":"Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: A multicentre study","volume":"142","author":"Postuma","year":"2019","journal-title":"Brain"},{"key":"10.3233\/JPD-223228_ref56","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.sleep.2012.10.009","article-title":"Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: A 16-year update on a previously reported series","volume":"14","author":"Schenck","year":"2013","journal-title":"Sleep Med"},{"key":"10.3233\/JPD-223228_ref57","doi-asserted-by":"crossref","first-page":"e1710","DOI":"10.1212\/WNL.0000000000006439","article-title":"Novel biomarker signatures for idiopathic REM sleep behavior disorder: A proteomic and system biology approach","volume":"91","author":"Mondello","year":"2018","journal-title":"Neurology"},{"key":"10.3233\/JPD-223228_ref58","doi-asserted-by":"crossref","first-page":"480","DOI":"10.3389\/fimmu.2019.00480","article-title":"CSF cytokines in aging, multiple sclerosis, and dementia","volume":"10","author":"Hu","year":"2019","journal-title":"Front Immunol"},{"key":"10.3233\/JPD-223228_ref59","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/1471-2377-14-113","article-title":"Potential biomarkers relating pathological proteins, neuroinflammatory factors and free radicals in PD patients with cognitive impairment: A cross-sectional study","volume":"14","author":"Yu","year":"2014","journal-title":"BMC Neurol"},{"key":"10.3233\/JPD-223228_ref60","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1212\/WNL.0000000000002151","article-title":"Increased CSF biomarkers of angiogenesis in Parkinson disease","volume":"85","author":"Janelidze","year":"2015","journal-title":"Neurology"},{"key":"10.3233\/JPD-223228_ref61","doi-asserted-by":"crossref","first-page":"13276","DOI":"10.1038\/s41598-018-31517-z","article-title":"Cerebrospinal fluid concentrations of inflammatory markers in Parkinson\u2019s disease and atypical parkinsonian disorders","volume":"8","author":"Hall","year":"2018","journal-title":"Sci Rep"},{"key":"10.3233\/JPD-223228_ref62","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.bbi.2013.07.007","article-title":"Cerebrospinal fluid inflammatory markers in Parkinson\u2019s disease - Associations with depression, fatigue, and cognitive impairment","volume":"33","author":"Lindqvist","year":"2013","journal-title":"Brain Behav Immun"},{"key":"10.3233\/JPD-223228_ref64","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1093\/brain\/awab306","article-title":"Imaging protein aggregates in the serum and cerebrospinal fluid in Parkinson\u2019s disease","volume":"145","author":"Lobanova","year":"2021","journal-title":"Brain"},{"key":"10.3233\/JPD-223228_ref65","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.bbi.2019.06.042","article-title":"Toll-like receptors and their therapeutic potential in Parkinson\u2019s disease and \u03b1-synucleinopathies","volume":"81","author":"Kouli","year":"2019","journal-title":"Brain Behav Immun"},{"key":"10.3233\/JPD-223228_ref66","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.cell.2016.11.018","article-title":"Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson\u2019s disease","volume":"167","author":"Sampson","year":"2016","journal-title":"Cell"},{"key":"10.3233\/JPD-223228_ref67","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41531-016-0002-0","article-title":"The gut-brain axis: Is intestinal inflammation a silent driver of Parkinson\u2019s disease pathogenesis?","volume":"3","author":"Houser","year":"2017","journal-title":"NPJ Parkinsons Dis"},{"key":"10.3233\/JPD-223228_ref68","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jpsychires.2006.01.010","article-title":"Altered lymphocyte distribution in Alzheimer\u2019s disease","volume":"41","author":"Richartz-Salzburger","year":"2007","journal-title":"J Psychiatr Res"},{"key":"10.3233\/JPD-223228_ref69","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3233\/JAD-2009-1015","article-title":"Dramatic shifts in circulating CD4 but not CD8 T cell subsets in mild Alzheimer\u2019s disease","volume":"17","author":"Larbi","year":"2009","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JPD-223228_ref70","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41586-019-1895-7","article-title":"Clonally expanded CD8 T cells patrol the cerebrospinal fluid in Alzheimer\u2019s disease","volume":"577","author":"Gate","year":"2020","journal-title":"Nature"},{"key":"10.3233\/JPD-223228_ref71","doi-asserted-by":"crossref","first-page":"77921","DOI":"10.1371\/journal.pone.0077921","article-title":"Decreased proportion of cytomegalovirus specific CD8 T-cells but no signs of general immunosenescence in Alzheimer\u2019s disease.e","volume":"8","author":"Westman","year":"2013","journal-title":"PLoS One"},{"key":"10.3233\/JPD-223228_ref72","doi-asserted-by":"crossref","first-page":"e96779","DOI":"10.1371\/journal.pone.0096779","article-title":"Increased inflammatory response in cytomegalovirus seropositive patients with Alzheimer\u2019s disease","volume":"9","author":"Westman","year":"2014","journal-title":"PLoS One"},{"key":"10.3233\/JPD-223228_ref73","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1093\/gerona\/glw053","article-title":"Meta-analysis of telomere length in Alzheimer\u2019s disease","volume":"71","author":"Forero","year":"2016","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.3233\/JPD-223228_ref74","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.exger.2016.01.002","article-title":"Telomere length in Parkinson\u2019s disease: A meta-analysis","volume":"75","author":"Forero","year":"2016","journal-title":"Exp Gerontol"},{"key":"10.3233\/JPD-223228_ref75","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/nature22815","article-title":"T cells from patients with Parkinson\u2019s disease recognize \u03b1-synuclein peptides","volume":"546","author":"Sulzer","year":"2017","journal-title":"Nature"},{"key":"10.3233\/JPD-223228_ref76","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1038\/s41467-020-15626-w","article-title":"\u03b1-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson\u2019s disease","volume":"11","author":"Lindestam Arlehamn","year":"2020","journal-title":"Nat Commun"},{"key":"10.3233\/JPD-223228_ref77","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41598-020-79726-9","article-title":"The TCR repertoire of \u03b1-synuclein-specific T cells in Parkinson\u2019s disease is surprisingly diverse","volume":"11","author":"Singhania","year":"2021","journal-title":"Sci Rep"},{"key":"10.3233\/JPD-223228_ref78","doi-asserted-by":"crossref","first-page":"815","DOI":"10.3389\/fneur.2018.00815","article-title":"A systematic review and meta-analysis of alpha synuclein auto-antibodies in Parkinson\u2019s disease","volume":"9","author":"Scott","year":"2018","journal-title":"Front Neurol"},{"key":"10.3233\/JPD-223228_ref79","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1136\/jnnp.2008.162883","article-title":"Association of the human leucocyte antigen region with susceptibility to Parkinson\u2019s disease","volume":"81","author":"Saiki","year":"2010","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.3233\/JPD-223228_ref80","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/ng.642","article-title":"Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson\u2019s disease","volume":"42","author":"Hamza","year":"2010","journal-title":"Nat Genet"},{"key":"10.3233\/JPD-223228_ref81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2009.12.017","article-title":"Apoptosis of peripheral blood lymphocytes in Parkinson patients","volume":"38","author":"Calopa","year":"2010","journal-title":"Neurobiol Dis"},{"key":"10.3233\/JPD-223228_ref82","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1681\/ASN.2019080847","article-title":"Terminally differentiated effector memory CD8+T cells identify kidney transplant recipients at high risk of graft failure","volume":"31","author":"Jacquemont","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"10.3233\/JPD-223228_ref83","doi-asserted-by":"crossref","first-page":"e0150945","DOI":"10.1371\/journal.pone.0150945","article-title":"T-lymphocytes traffic into the brain across the blood-CSF barrier: Evidence using a reconstituted choroid plexus epithelium","volume":"11","author":"Strazielle","year":"2016","journal-title":"PLoS One"},{"key":"10.3233\/JPD-223228_ref84","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.3389\/fneur.2018.01081","article-title":"Immune cell activation in the cerebrospinal fluid of patients with Parkinson\u2019s disease","volume":"9","author":"Schr\u00f6der","year":"2018","journal-title":"Front Neurol"},{"key":"10.3233\/JPD-223228_ref85","first-page":"182","article-title":"Infiltration of CD4+lymphocytes into the brain contributes to neurodegeneration in a mouse model of Parkinson disease","volume":"119","author":"Brochard","year":"2009","journal-title":"J Clin Invest"},{"key":"10.3233\/JPD-223228_ref86","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s40478-020-01083-5","article-title":"Neuroinflammation and protein pathology in Parkinson\u2019s disease dementia","volume":"8","author":"Kouli","year":"2020","journal-title":"Acta Neuropathol Commun"},{"key":"10.3233\/JPD-223228_ref87","doi-asserted-by":"crossref","first-page":"3717","DOI":"10.1093\/brain\/awaa269","article-title":"CD8 T cell nigral infiltration precedes synucleinopathy in early stages of Parkinson\u2019s disease","volume":"143","author":"Galiano-Landeira","year":"2020","journal-title":"Brain"},{"key":"10.3233\/JPD-223228_ref88","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1186\/s12877-021-02128-7","article-title":"Lifestyle exercise attenuates immunosenescence; flow cytometry analysis","volume":"21","author":"Tylutka","year":"2021","journal-title":"BMC Geriatr"},{"key":"10.3233\/JPD-223228_ref89","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/s41577-019-0177-9","article-title":"Can physical activity ameliorate immunosenescence and thereby reduce age-related multi-morbidity?","volume":"19","author":"Duggal","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"10.3233\/JPD-223228_ref90","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/mds.21922","article-title":"The effectiveness of exercise interventions for people with Parkinson\u2019s disease: A systematic review and meta-analysis","volume":"23","author":"Goodwin","year":"2008","journal-title":"Mov Disord"},{"key":"10.3233\/JPD-223228_ref91","doi-asserted-by":"crossref","first-page":"685","DOI":"10.3233\/JPD-160790","article-title":"The effects of physical activity in Parkinson\u2019s disease: A review","volume":"6","author":"Lauz\u00e9","year":"2016","journal-title":"J Parkinsons Dis"},{"key":"10.3233\/JPD-223228_ref92","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1002\/mds.25377","article-title":"Nonpharmacological enhancement of cognitive function in Parkinson\u2019s disease: A systematic review","volume":"28","author":"Hindle","year":"2013","journal-title":"Mov Disord"},{"key":"10.3233\/JPD-223228_ref93","doi-asserted-by":"crossref","first-page":"e0193113","DOI":"10.1371\/journal.pone.0193113","article-title":"Effects of physical exercise programs on cognitive function in Parkinson\u2019s disease patients: A systematic review of randomized controlled trials of the last 10 years","volume":"13","author":"da Silva","year":"2018","journal-title":"PLoS One"},{"key":"10.3233\/JPD-223228_ref94","doi-asserted-by":"crossref","first-page":"e0181515","DOI":"10.1371\/journal.pone.0181515","article-title":"Effectiveness of physical activity on patients with depression and Parkinson\u2019s disease: A systematic review","volume":"12","author":"Wu","year":"2017","journal-title":"PLoS One"}],"container-title":["Journal of Parkinson's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JPD-223228","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:51:47Z","timestamp":1777611107000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JPD-223228"}},"subtitle":[],"editor":[{"given":"Bastiaan R.","family":"Bloem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Patrik","family":"Brundin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Eng King","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Ashley","family":"Harms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Cecilia","family":"Lindestam Arlehamn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]},{"given":"Caroline","family":"Williams-Gray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,9,27]]},"references-count":92,"journal-issue":{"issue":"s1"},"URL":"https:\/\/doi.org\/10.3233\/jpd-223228","relation":{},"ISSN":["1877-7171","1877-718X"],"issn-type":[{"value":"1877-7171","type":"print"},{"value":"1877-718X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,27]]}}}