{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:00:13Z","timestamp":1777395613868,"version":"3.51.4"},"reference-count":46,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2022,7,19]]},"abstract":"<jats:p>Background: Platelet proteins may be associated with Alzheimer\u2019s disease (AD) pathology. Objective: To investigate the relationship between platelet proteins and cerebrospinal fluid (CSF) biomarkers of AD and cognition in individuals with memory decline to identify effective screening methods for detecting the early stages of the disease. Methods: We classified 68 participants with subjective memory decline according to the ATN framework determined by CSF amyloid-\u03b2 (A), CSF p-tau (T), and t-tau (N). All participants underwent Mini-Mental State Examination (MMSE) and platelet-related protein content testing. Results: Eighteen participants had normal AD biomarkers (NCs), 24 subjects had non-AD pathologic changes (non-AD), and 26 subjects fell within the Alzheimer\u2019s continuum (AD). The platelet amyloid-\u03b2 protein precursor (A\u03b2PP) ratio in the AD group was significantly lower than in the non-AD and NCs groups, and positively correlated with MMSE scores and CSF amyloid-\u03b242 level, which could affect MMSE scores through CSF amyloid-\u03b242. Levels of platelet phosphorylated-tau 231 and ser396\/404 phosphorylated tau were elevated in both AD and non-AD compared to NCs. Additionally, the receiver operating characteristic analysis demonstrated that the platelet A\u03b2PP ratio was a sensitive identifier for differentiating the AD from NCs (AUC\u200a=\u200a0.846) and non-AD (AUC\u200a=\u200a0.768). And ser396\/404 phosphorylated tau could distinguish AD from NCs. Conclusion: Our study was the first to find an association between platelet A\u03b2PP ratio and CSF biomarkers of AD, which contribute to the understanding of the peripheral changes in AD. These findings may help to discover potential feasible and effective screening tools for AD.<\/jats:p>","DOI":"10.3233\/jad-220122","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T12:04:03Z","timestamp":1654257843000},"page":"589-599","source":"Crossref","is-referenced-by-count":4,"title":["Platelet-Derived Amyloid-\u03b2 Protein Precursor as a Biomarker of Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"88","author":[{"given":"Qing","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, The Affiliated ZhongDa Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yachen","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated ZhongDa Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyang","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyu","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated ZhongDa Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated ZhongDa Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingping","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunming","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated ZhongDa Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, China"},{"name":"The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Affiliated ZhongDa Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, China"},{"name":"The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing, China"},{"name":"The Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-220122_ref1","first-page":"16217","article-title":"Cognitive symptoms of Alzheimer\u2019s disease: Clinical management and prevention","volume":"367","author":"Joe","year":"2019","journal-title":"BMJ"},{"key":"10.3233\/JAD-220122_ref2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S1474-4422(19)30290-X","article-title":"Dementia in China: Epidemiology, clinical management, and research advances.","volume":"19","author":"Jia","year":"2020","journal-title":"Lancet Neurol"},{"key":"10.3233\/JAD-220122_ref3","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jalz.2017.12.006","article-title":"The cost of Alzheimer\u2019s disease in China and re-estimation of costs worldwide.","volume":"14","author":"Jia","year":"2018","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220122_ref4","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.jalz.2018.01.001","article-title":"National Institute on Aging - Alzheimer\u2019s Association Research Framework lays the groundwork for deeper understanding of Alzheimer\u2019s disease.","volume":"14","author":"Knopman","year":"2018","journal-title":"Alzheimers Dement"},{"key":"10.3233\/JAD-220122_ref5","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-220122_ref6","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jns.2005.09.002","article-title":"Platelet amyloid precursor protein processing: A bio-marker for Alzheimer\u2019s disease","volume":"240","author":"Tang","year":"2006","journal-title":"J Neurol Sci"},{"key":"10.3233\/JAD-220122_ref7","doi-asserted-by":"crossref","first-page":"8815","DOI":"10.1007\/s12035-018-1039-3","article-title":"Platelet proteomic analysis revealed differential pattern of cytoskeletal- and immune-related proteins at early stages of Alzheimer\u2019s disease","volume":"55","author":"Gonzalez-Sanchez","year":"2018","journal-title":"Mol Neurobiol"},{"key":"10.3233\/JAD-220122_ref8","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1001\/archneur.55.9.1195","article-title":"Differential level of platelet amyloid \u03b2 precursor protein isoforms: An early marker for Alzheimer disease","volume":"55","author":"Di Luca","year":"1998","journal-title":"Arch Neurol"},{"key":"10.3233\/JAD-220122_ref9","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1001\/archneur.1997.00550140019007","article-title":"Altered amyloid protein processing in platelets of patients with Alzheimer disease","volume":"54","author":"Rosenberg","year":"1997","journal-title":"Arch Neurol"},{"key":"10.3233\/JAD-220122_ref10","first-page":"664","article-title":"Platelet amyloid-beta protein precursor (AbetaPP) ratio and phosphorylated tau as promising indicators for early Alzheimer\u2019s disease","volume":"75","author":"Shi","year":"2020","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"10.3233\/JAD-220122_ref11","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1212\/WNL.54.10.1907","article-title":"Platelet APP isoform ratios correlate with declining cognition in AD","volume":"54","author":"Baskin","year":"2000","journal-title":"Neurology"},{"key":"10.3233\/JAD-220122_ref12","doi-asserted-by":"crossref","first-page":"e13358","DOI":"10.1111\/acel.13358","article-title":"Platelet biomarkers for a descending cognitive function: A proteomic approach","volume":"20","author":"Yu","year":"2021","journal-title":"Aging Cell"},{"key":"10.3233\/JAD-220122_ref13","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1007\/s00406-018-0905-3","article-title":"Protein levels of ADAM10, BACE1, and PSEN1 in platelets and leukocytes of Alzheimer\u2019s disease patients","volume":"269","author":"Bram","year":"2019","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"10.3233\/JAD-220122_ref14","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1007\/s00702-012-0807-x","article-title":"Reduced platelet amyloid precursor protein ratio (APP ratio) predicts conversion from mild cognitive impairment to Alzheimer\u2019s disease","volume":"119","author":"Zainaghi","year":"2012","journal-title":"J Neural Transm (Vienna)"},{"key":"10.3233\/JAD-220122_ref15","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.3233\/JAD-180181","article-title":"Platelets: Peripheral biomarkers of dementia?","volume":"63","author":"Akingbade","year":"2018","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220122_ref16","doi-asserted-by":"crossref","first-page":"95","DOI":"10.5498\/wjp.v2.i6.95","article-title":"Platelet biomarkers in Alzheimer\u2019s disease","volume":"2","author":"Talib","year":"2012","journal-title":"World J Psychiatry"},{"key":"10.3233\/JAD-220122_ref17","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.exger.2009.08.004","article-title":"Blood cell markers in Alzheimer disease: Amyloid precursor protein form ratio in platelets","volume":"45","author":"Borroni","year":"2010","journal-title":"Exp Gerontol"},{"key":"10.3233\/JAD-220122_ref18","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1111\/j.1538-7836.2007.02690.x","article-title":"Proteomic analysis of platelet alpha-granules using mass spectrometry","volume":"5","author":"Maynard","year":"2007","journal-title":"J Thromb Haemost"},{"key":"10.3233\/JAD-220122_ref19","doi-asserted-by":"crossref","first-page":"e7627","DOI":"10.1371\/journal.pone.0007627","article-title":"Proteomic and phospho-proteomic profile of human platelets in basal, resting state: Insights into integrin signaling","volume":"4","author":"Qureshi","year":"2009","journal-title":"PLoS One"},{"key":"10.3233\/JAD-220122_ref20","doi-asserted-by":"crossref","first-page":"571083","DOI":"10.3389\/fimmu.2020.571083","article-title":"On the role of platelet-generated amyloid beta peptides in certain amyloidosis health complications","volume":"11","author":"Inyushin","year":"2020","journal-title":"Front Immunol"},{"key":"10.3233\/JAD-220122_ref21","doi-asserted-by":"crossref","first-page":"101783","DOI":"10.1016\/j.pneurobio.2020.101783","article-title":"Platelets promote epileptic seizures by modulating brain serotonin level, enhancing neuronal electric activity, and contributing to neuroinflammation and oxidative stress","volume":"188","author":"Kopeikina","year":"2020","journal-title":"Prog Neurobiol"},{"key":"10.3233\/JAD-220122_ref22","doi-asserted-by":"crossref","first-page":"7644","DOI":"10.18632\/aging.202662","article-title":"Platelets transport \u03b2-amyloid from the peripheral blood into the brain by destroying the blood-brain barrier to accelerate the process of Alzheimer\u2019s disease in mouse models","volume":"13","author":"Wu","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"10.3233\/JAD-220122_ref23","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-3-030-05542-4_4","article-title":"Lymphocytes, platelets, erythrocytes, and exosomes as possible biomarkers for Alzheimer\u2019s disease clinical diagnosis","volume":"1118","author":"Pluta","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"10.3233\/JAD-220122_ref24","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3389\/fncel.2015.00065","article-title":"Role of amyloid peptides in vascular dysfunction and platelet dysregulation in Alzheimer\u2019s disease","volume":"9","author":"Canobbio","year":"2015","journal-title":"Front Cell Neurosci"},{"key":"10.3233\/JAD-220122_ref25","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1212\/WNL.0000000000002923","article-title":"A\/T\/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers","volume":"87","author":"Jack","year":"2016","journal-title":"Neurology"},{"key":"10.3233\/JAD-220122_ref26","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1373\/clinchem.2009.130518","article-title":"Amyloid-beta(1-42), total tau, and phosphorylated tau as cerebrospinal fluid biomarkers for the diagnosis of Alzheimer disease","volume":"56","author":"Mulder","year":"2010","journal-title":"Clin Chem"},{"key":"10.3233\/JAD-220122_ref27","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1007\/s11682-018-9923-z","article-title":"Amygdala connectivity mediates the association between anxiety and depression in patients with major depressive disorder","volume":"13","author":"He","year":"2019","journal-title":"Brain Imaging Behav"},{"key":"10.3233\/JAD-220122_ref28","doi-asserted-by":"crossref","first-page":"117428","DOI":"10.1016\/j.neuroimage.2020.117428","article-title":"Identification of microRNA-9 linking the effects of childhood maltreatment on depression using amygdala connectivity","volume":"224","author":"He","year":"2020","journal-title":"Neuroimage"},{"key":"10.3233\/JAD-220122_ref29","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3","article-title":"Index for rating diagnostic tests","volume":"3","author":"Youden","year":"1950","journal-title":"Cancer"},{"key":"10.3233\/JAD-220122_ref30","doi-asserted-by":"crossref","first-page":"e46","DOI":"10.1212\/WNL.0000000000009724","article-title":"ATN classification and clinical progression in subjective cognitive decline: The SCIENCe project","volume":"95","author":"Ebenau","year":"2020","journal-title":"Neurology"},{"key":"10.3233\/JAD-220122_ref31","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.3233\/JAD-160813","article-title":"Protein expression of BACE1 is downregulated by donepezil in Alzheimer\u2019s disease platelets","volume":"55","author":"Sarno","year":"2017","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220122_ref32","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3233\/JAD-2007-11111","article-title":"Correlation between platelet amyloid precursor protein isoform ratio and cognition in Alzheimer\u2019s disease","volume":"11","author":"Liu","year":"2007","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220122_ref33","doi-asserted-by":"crossref","first-page":"1948","DOI":"10.1038\/mp.2017.204","article-title":"Blood-derived amyloid-\u03b2 protein induces Alzheimer\u2019s disease pathologies","volume":"23","author":"Bu","year":"2018","journal-title":"Mol Psychiatry"},{"key":"10.3233\/JAD-220122_ref34","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3389\/fnagi.2019.00151","article-title":"Decoding the role of platelets and related microRNAs in aging and neurodegenerative disorders","volume":"11","author":"Espinosa-Parrilla","year":"2019","journal-title":"Front Aging Neurosci"},{"key":"10.3233\/JAD-220122_ref35","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00213-007-0748-5","article-title":"Abnormal APP processing in platelets of patients with Alzheimer\u2019s disease: Correlations with membrane fluidity and cognitive decline","volume":"192","author":"Zainaghi","year":"2007","journal-title":"Psychopharmacology (Berl)"},{"key":"10.3233\/JAD-220122_ref36","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1097\/00002093-200401000-00006","article-title":"Predicting cognitive decline in Alzheimer disease. Role of platelet amyloid precursor protein","volume":"18","author":"Borroni","year":"2004","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"10.3233\/JAD-220122_ref37","doi-asserted-by":"crossref","first-page":"17036","DOI":"10.1074\/jbc.M006285200","article-title":"Amyloid precursor protein and amyloid beta peptide in human platelets. Role of cyclooxygenase and protein kinase C","volume":"276","author":"Skovronsky","year":"2001","journal-title":"J Biol Chem"},{"key":"10.3233\/JAD-220122_ref38","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1161\/STROKEAHA.112.670976","article-title":"Brain and circulating levels of Abeta1-40 differentially contribute to vasomotor dysfunction in the mouse brain","volume":"44","author":"Park","year":"2013","journal-title":"Stroke"},{"key":"10.3233\/JAD-220122_ref39","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1161\/CIRCRESAHA.117.311054","article-title":"Brain perivascular macrophages initiate the neurovascular dysfunction of Alzheimer Abeta peptides","volume":"121","author":"Park","year":"2017","journal-title":"Circ Res"},{"key":"10.3233\/JAD-220122_ref40","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/S0306-9877(02)00380-8","article-title":"Does increased platelet release of A\u03b2 peptide contribute to brain abnormalities in individuals with depression?","volume":"60","author":"Pomara","year":"2003","journal-title":"Med Hypotheses"},{"key":"10.3233\/JAD-220122_ref41","doi-asserted-by":"crossref","first-page":"101420","DOI":"10.1016\/j.arr.2021.101420","article-title":"Can platelet activation result in increased plasma Abeta levels and contribute to the pathogenesis of Alzheimer\u2019s disease?","volume":"71","author":"Carbone","year":"2021","journal-title":"Ageing Res Rev"},{"key":"10.3233\/JAD-220122_ref42","first-page":"750","article-title":"Platelet APP processing: Is it a tool to explore the pathophysiology of Alzheimer\u2019s disease? A systematic review","volume":"11","author":"Carbone","year":"2021","journal-title":"Life (Basel)"},{"key":"10.3233\/JAD-220122_ref43","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3233\/JAD-2011-101641","article-title":"Human platelets tau: A potential peripheral marker for Alzheimer\u2019s disease","volume":"25","author":"Neumann","year":"2011","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-220122_ref44","doi-asserted-by":"crossref","first-page":"e12921","DOI":"10.15252\/emmm.202012921","article-title":"Novel tau biomarkers phosphorylatedat T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer\u2019s continuum when only subtle changes in Abeta pathology are detected","volume":"12","author":"Suarez-Calvet","year":"2020","journal-title":"EMBO Mol Med"},{"key":"10.3233\/JAD-220122_ref45","doi-asserted-by":"crossref","first-page":"190","DOI":"10.3390\/biomedicines9020190","article-title":"Critical molecular and cellular contributors to tau pathology","volume":"9","author":"Song","year":"2021","journal-title":"Biomedicines"},{"key":"10.3233\/JAD-220122_ref46","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/S1474-4422(13)70090-5","article-title":"Tau pathology and neurodegeneration","volume":"12","author":"Spillantini","year":"2013","journal-title":"Lancet Neurol"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-220122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:06:15Z","timestamp":1777370775000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-220122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,19]]},"references-count":46,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.3233\/jad-220122","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,19]]}}}