{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:49:52Z","timestamp":1783471792972,"version":"3.55.0"},"reference-count":25,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,5,17]]},"abstract":"<jats:p>Background: The G protein-coupled receptor P2RY2 protein of the purinergic receptor family is involved in the pathogenesis of Alzheimer\u2019s disease (AD). Naturally occurring antibodies against P2RY2 (NAbs-P2RY2) are present in human plasma, with their clinical relevance in AD unknown. Objective: To explore the alteration of NAbs-P2RY2 in AD patients and its associations with biomarkers and cognition of AD patients. Methods: The levels of naturally occurring antibodies against the four extracellular domains of P2RY2 (NAbs-P2RY2-1, NAbs-P2RY2-2, NAbs-P2RY2-3, and NAbs-P2RY2-4) were measured in the plasma of 55 AD patients, 28 non-AD dementia patients, and 70 cognitively normal participants. The correlations of autoantibody levels with cognitive scale scores, AD plasma biomarkers, and brain amyloid burden were examined. Results: NAbs-P2RY2-1, NAbs-P2RY2-3, and NAbs-P2RY2-4 were reduced in AD patients. Plasma levels of NAbs-P2RY2-2 and NAbs-P2RY2-3 levels were positively associated with cognitive and functional performances. Among these antibodies, plasma NAbs-P2RY2-2 levels were positively associated with plasma amyloid-\u03b2 42 levels. While plasma NAbs-P2RY2-3 levels were negatively associated with brain amyloid burden in AD patients. Conclusion: These findings indicate an alteration of humoral immunity against P2RY2 in AD patients. Further mechanistical investigations are needed to reveal the role of NAbs-P2RY2 in the pathogenesis of AD.<\/jats:p>","DOI":"10.3233\/jad-215611","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T18:24:53Z","timestamp":1647973493000},"page":"711-719","source":"Crossref","is-referenced-by-count":6,"title":["Circulating Naturally Occurring Antibodies to P2RY2 Are Decreased in Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"87","author":[{"given":"Jie-Ming","family":"Jian","sequence":"first","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Yu","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China"},{"name":"Shigatse Branch, Xinqiao Hospital, Third Military Medical University, Shigatse, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Ying","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Wan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui-Hua","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Rong","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Jiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China"},{"name":"Key Laboratory of Ageing and Brain Diseases, Chongqing, China"},{"name":"Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-215611_ref1","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"10.3233\/JAD-215611_ref2","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA Research Framework: Toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-215611_ref3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-319-12679-1_1","article-title":"Neuroanatomy and pathology of sporadic Alzheimer\u2019s disease","volume":"215","author":"Braak","year":"2015","journal-title":"Adv Anat Embryol Cell Biol"},{"key":"10.3233\/JAD-215611_ref4","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.drudis.2013.07.020","article-title":"Immunity and Alzheimer\u2019s disease: Immunological perspectives on the development of novel therapies","volume":"18","author":"Liu","year":"2013","journal-title":"Drug Discov Today"},{"key":"10.3233\/JAD-215611_ref5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.dadm.2016.03.002","article-title":"Detection of Alzheimer\u2019s disease at mild cognitive impairment and disease progression using autoantibodies as blood-based biomarkers","volume":"3","author":"DeMarshall","year":"2016","journal-title":"Alzheimers Dement (Amst)"},{"key":"10.3233\/JAD-215611_ref6","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1006\/bbrc.1995.1798","article-title":"Cloning of rat and mouse P2Y purinoceptors","volume":"211","author":"Tokuyama","year":"1995","journal-title":"Biochem Biophys Res Commun"},{"key":"10.3233\/JAD-215611_ref7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0014-2999(02)01756-9","article-title":"P2Y and P2X purinoceptor mediated Ca2+signalling in glial cell pathology in the central nervous system","volume":"447","author":"James","year":"2002","journal-title":"Eur J Pharmacol"},{"key":"10.3233\/JAD-215611_ref8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/sj.bjp.0705044","article-title":"P2Ys go neuronal: Modulation of Ca2+and K+channels by recombinant receptors","volume":"138","author":"Boehm","year":"2003","journal-title":"Br J Pharmacol"},{"key":"10.3233\/JAD-215611_ref9","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s11302-018-9629-0","article-title":"Role of purinergic receptors in the Alzheimer\u2019s disease","volume":"14","author":"Cie\u015blak","year":"2018","journal-title":"Purinergic Signal"},{"key":"10.3233\/JAD-215611_ref10","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1111\/j.1471-4159.2009.06048.x","article-title":"Interleukin-1beta enhances nucleotide-induced and alpha-secretase-dependent amyloid precursor protein processing in rat primary cortical neurons via up-regulation of the P2Y(2) receptor","volume":"109","author":"Kong","year":"2009","journal-title":"J Neurochem"},{"key":"10.3233\/JAD-215611_ref11","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1016\/j.febslet.2011.05.048","article-title":"Opposite effects of P2X7 and P2Y2 nucleotide receptors on \u03b1-secretase-dependent APP processing in Neuro-2a cells","volume":"585","author":"Le\u00f3n-Otegui","year":"2011","journal-title":"FEBS Lett"},{"key":"10.3233\/JAD-215611_ref12","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1007\/s00702-008-0067-y","article-title":"Selective loss of P2Y2 nucleotide receptor immunoreactivity is associated with Alzheimer\u2019s disease neuropathology","volume":"115","author":"Lai","year":"2008","journal-title":"J Neural Transm (Vienna)"},{"key":"10.3233\/JAD-215611_ref13","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1242\/jcs.03441","article-title":"The P2Y2 nucleotide receptor requires interaction with alpha v integrins to access and activate G12","volume":"120","author":"Liao","year":"2007","journal-title":"J Cell Sci"},{"key":"10.3233\/JAD-215611_ref14","doi-asserted-by":"crossref","first-page":"2866","DOI":"10.1523\/JNEUROSCI.4970-06.2007","article-title":"Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway","volume":"27","author":"Shankar","year":"2007","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-215611_ref15","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s12035-010-8115-7","article-title":"P2Y2 nucleotide receptor-mediated responses in brain cells","volume":"41","author":"Peterson","year":"2010","journal-title":"Mol Neurobiol"},{"key":"10.3233\/JAD-215611_ref16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"\u201cMini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res"},{"key":"10.3233\/JAD-215611_ref17","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1212\/WNL.43.11.2412-a","article-title":"The Clinical Dementia Rating (CDR): Current version and scoring rules","volume":"43","author":"Morris","year":"1993","journal-title":"Neurology"},{"key":"10.3233\/JAD-215611_ref18","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1001\/archneurol.2010.115","article-title":"Validation of the new interpretive guidelines for the clinical dementia rating scale sum of boxes score in the national Alzheimer\u2019s coordinating center database","volume":"67","author":"O\u2019Bryant","year":"2010","journal-title":"Arch Neurol"},{"key":"10.3233\/JAD-215611_ref19","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J Am Geriatr Soc"},{"key":"10.3233\/JAD-215611_ref20","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/j.1532-5415.1975.tb00927.x","article-title":"A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients","volume":"23","author":"Pfeiffer","year":"1975","journal-title":"J Am Geriatr Soc"},{"key":"10.3233\/JAD-215611_ref21","doi-asserted-by":"crossref","first-page":"eabb0457","DOI":"10.1126\/sciadv.abb0457","article-title":"Association of naturally occurring antibodies to \u03b2-amyloid with cognitive decline and cerebral amyloidosis in Alzheimer\u2019s disease","volume":"7","author":"Liu","year":"2021","journal-title":"Sci Adv"},{"key":"10.3233\/JAD-215611_ref22","doi-asserted-by":"crossref","unstructured":"(2016) 2016 Alzheimer\u2019s disease facts and figures. Alzheimers Dement 12, 459\u2013509.","DOI":"10.1016\/j.jalz.2016.03.001"},{"key":"10.3233\/JAD-215611_ref23","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1136\/jnnp-2016-313476","article-title":"Association between naturally occurring anti-amyloid \u03b2 autoantibodies and medial temporal lobe atrophy in Alzheimer\u2019s disease","volume":"88","author":"Kimura","year":"2017","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.3233\/JAD-215611_ref24","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1002\/ana.23857","article-title":"Anti-amyloid \u03b2 autoantibodies in cerebral amyloid angiopathy-related inflammation: Implications for amyloid-modifying therapies","volume":"73","author":"Piazza","year":"2013","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-215611_ref25","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/j.1471-4159.2012.07700.x","article-title":"Nucleotides released from A\u03b21-42-treated microglial cells increase cell migration and A\u03b21-42 uptake through P2Y2 receptor activation","volume":"121","author":"Kim","year":"2012","journal-title":"J Neurochem"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-215611","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:05:46Z","timestamp":1777370746000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-215611"}},"subtitle":[],"editor":[{"given":"Jin-Tai","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,5,17]]},"references-count":25,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/jad-215611","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,17]]}}}