{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T07:03:06Z","timestamp":1780124586327,"version":"3.54.0"},"reference-count":27,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["IIRG\u201008\u201088733"],"award-info":[{"award-number":["IIRG\u201008\u201088733"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P20\u2010AG068082"],"award-info":[{"award-number":["P20\u2010AG068082"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>\n                      We test the hypothesis that high levels of neuroplasticity in the context of Alzheimer's disease (AD) risk factors are involved in AD pathogenesis by investigating interactions between cerebrospinal fluid (CSF) levels of growth\u2010associated protein\u201043 (GAP\u201043) and AD risk factors (female sex, cerebrovascular risk, mild cognitive impairment,\n                      <jats:italic>apolipoprotein E<\/jats:italic>\n                      [\n                      <jats:italic>APOE<\/jats:italic>\n                      ] \u03b54 genotype, amyloid positivity) on CSF biomarkers of AD pathology (amyloid beta 42\/40[A\u03b242\/40], phosphorylated tau (p\u2010tau)) and neurodegeneration (tau).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Baseline GAP\u201043 levels in 161 non\u2010demented older adults were related to cross\u2010sectional and longitudinal (mean follow\u2010up = 4 years) CSF biomarkers of AD, adjusting for covariates, with\n                      <jats:italic>GAP\u201043 x AD risk factor<\/jats:italic>\n                      interaction terms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Higher GAP\u201043 was cross\u2010sectionally related to all AD biomarkers (\n                      <jats:italic>p<\/jats:italic>\n                      \u2010values &lt; 0.0001) and predicted longitudinal reductions in A\u03b242 (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.0001). Associations were stronger in AD risk groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>We found strong support linking increased levels of neuroplasticity in the context of AD risk factors to the pathological cascade of AD over a 4\u2010year mean follow\u2010up period.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Cerebrospinal fluid growth\u2010associated protein\u201043 (GAP\u201043) is associated with Alzheimer's disease (AD) biomarkers cross\u2010sectionally and longitudinally.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>GAP\u201043 interacts with AD risk factors to predict AD biomarkers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Increased neuroplastic activity may play a role in AD pathogenesis.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70897","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T03:59:22Z","timestamp":1764388762000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased neuroplastic activity in the pathogenesis of Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Corey J.","family":"Bolton","sequence":"first","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine  Nashville Tennessee USA"},{"name":"Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine  Nashville Tennessee USA"},{"name":"Department of Biostatistics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney R.","family":"Wilhoite","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth E.","family":"Moore","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine  Nashville Tennessee USA"},{"name":"Department of Neurology Mass General Brigham  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"Houston","sequence":"additional","affiliation":[{"name":"Section of Surgical Sciences Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly R.","family":"Pechman","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine  Nashville Tennessee USA"},{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Peterson","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine  Nashville Tennessee USA"},{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omair A.","family":"Khan","sequence":"additional","affiliation":[{"name":"Vanderbilt Brain Institute Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Liu","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine  Nashville Tennessee USA"},{"name":"Department of Biostatistics Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Gifford","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology Boston University Chobanian &amp; Avedisian School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy at University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Lab Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Hohman","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine  Nashville Tennessee USA"},{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy at University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Lab Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology  London UK"},{"name":"UK Dementia Research Institute at UCL  London UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela L.","family":"Jefferson","sequence":"additional","affiliation":[{"name":"Vanderbilt Memory and Alzheimer's Center Vanderbilt University School of Medicine  Nashville Tennessee USA"},{"name":"Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"},{"name":"Department of Neurology Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0896\u20106273(00)81109\u20105"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2004.07.007"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1240\/dev.108712"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3738509"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.13.7657"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.08.006"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000051268"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa395"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012853"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12087"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.12.009"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.03.008"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.57.1.100"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000012257"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2018.02.009"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.274"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm\u20102021\u20100651"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2007.06.006"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.111203"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755\u20105949.2010.00221.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(92)90831\u2010s"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2015.04.040"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010012\u20108360\u2010z"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201020324\u20102"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201417"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1240\/jcs.01558"}],"container-title":["Alzheimer's &amp; Dementia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70897","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/alz.70897","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/alz.70897","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T06:39:03Z","timestamp":1780123143000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/alz.70897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":27,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/alz.70897"],"URL":"https:\/\/doi.org\/10.1002\/alz.70897","archive":["Portico"],"relation":{},"ISSN":["1552-5260","1552-5279"],"issn-type":[{"value":"1552-5260","type":"print"},{"value":"1552-5279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2025-05-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70897"}}