{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T14:49:38Z","timestamp":1791125378628,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T00:00:00Z","timestamp":1620864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Introduction: Biomarkers that reflect pathologic processes affecting neuronal function during preclinical and early stages of Alzheimer's disease (AD) are needed to aid drug development.<\/jats:p>\n                  <jats:p>\n                    Methods: A targeted, stable isotope, quantitative mass spectrometry\u2010based investigation of longitudinal changes in concentrations of previously identified candidate biomarkers was performed in cerebrospinal fluid (CSF) of Alzheimer's Disease Neuroimaging Initiative participants who were classified as cognitively normal (CN;\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a076) or with mild cognitive impairment (MCI;\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a0111) at baseline.\n                  <\/jats:p>\n                  <jats:p>Results: Of the candidate biomarkers, the CSF concentration of neuronal pentraxin 2 (NPTX2), a protein involved in synaptic function, exhibited rates of change that were significantly different between three comparison groups (i.e., CN vs. MCI participants; AD pathology positive vs. negative defined by phosphorylated tau181\/amyloid beta1\u201042 ratio; and clinical progressors vs. non\u2010progressors). The rate of change of NPTX2 also significantly correlated with declining cognition.<\/jats:p>\n                  <jats:p>Discussion: CSF NPTX2 concentration is a strong prognostic biomarker candidate of accelerated cognitive decline with potential use as a therapeutic target.<\/jats:p>","DOI":"10.1002\/alz.12353","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T12:29:24Z","timestamp":1620908964000},"page":"1976-1987","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Longitudinal CSF proteomics identifies NPTX2 as a prognostic biomarker of Alzheimer's disease"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3909-9760","authenticated-orcid":false,"given":"Ondrej","family":"Libiger","sequence":"first","affiliation":[{"name":"Janssen Research and Development  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leslie M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark H.","family":"Watson","sequence":"additional","affiliation":[{"name":"Caprion Biosciences  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus C.","family":"Nairn","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly L.","family":"Uma\u00f1a","sequence":"additional","affiliation":[{"name":"Foundation for the National Institutes of Health  North Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Biarnes","sequence":"additional","affiliation":[{"name":"Foundation for the National Institutes of Health  North Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa M.","family":"Canet\u2010Avil\u00e9s","sequence":"additional","affiliation":[{"name":"Foundation for the National Institutes of Health  North Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Clifford R.","family":"Jack","sequence":"additional","affiliation":[{"name":"Department of Radiology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick\u2010Andr\u00e9","family":"Breton","sequence":"additional","affiliation":[{"name":"Caprion Biosciences  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Cortes","sequence":"additional","affiliation":[{"name":"Caprion Biosciences  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Chelsky","sequence":"additional","affiliation":[{"name":"Caprion Biosciences  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Spellman","sequence":"additional","affiliation":[{"name":"Merck &amp; Co., Inc.  West Point Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan A.","family":"Baker","sequence":"additional","affiliation":[{"name":"Janssen Research and Development  Titusville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nandini","family":"Raghavan","sequence":"additional","affiliation":[{"name":"Janssen Research and Development  Titusville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William Z.","family":"Potter","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Alzheimer's Disease Neuroimaging Initiative (ADNI)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Foundation for the National Institutes of Health (FNIH) Biomarkers Consortium, Longitudinal CSF Proteomics Project Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132814"},{"key":"e_1_2_8_3_1","first-page":"1125.e1","article-title":"Synaptic protein deficits are associated with dementia irrespective of extreme old age","volume":"33","author":"Beeri MS","year":"2012","journal-title":"Neurobiol Aging"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu190"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30235-6"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2017.05.002"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.08.005"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70299-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.155"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_2_8_11_1","volume-title":"Predictive performance of CSF and imaging biomarkers in ADNI1\/GO\/2 MCI participants using the NIA\u2010AA Research Framework","author":"Shaw LM","year":"2018"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1932-x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000435556.21319.e4"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/prca.201400178"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.0086"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)00070-3"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0135365"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-9-22"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018850"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-8-39"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-017-0276-4"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.23798"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2019.11.002"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2012.1070"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2013.05.1769"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-54204-z"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv267"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-015-0142-1"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-015-0124-3"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005057"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1151-4"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.01.012"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00463-X"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2621"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.01.010"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.05.016"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2768-16.2016"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80782-5"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-11-04487.2002"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.02.020"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.04.024"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80974-5"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.07.148"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2019-322493"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12353","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.12353","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.12353","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T21:20:28Z","timestamp":1759872028000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.12353"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,13]]},"references-count":43,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1002\/alz.12353"],"URL":"https:\/\/doi.org\/10.1002\/alz.12353","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,13]]},"assertion":[{"value":"2021-01-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}