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OPN levels were examined as a function of amyloid beta (A\u03b2) and tau positivity. Survival analyses investigated the link between OPN and rate of conversion to AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In PREVENT\u2010AD, CSF OPN was positively correlated with synaptic biomarkers. In PREVENT\u2010AD and ADNI, OPN was elevated in CSF A\u03b2\n                      <jats:sub>42\/40<\/jats:sub>\n                      (+)\/total tau(+) and CSF A\u03b2\n                      <jats:sub>42\/40<\/jats:sub>\n                      (+)\/phosphorylated tau181(+) individuals. In ADNI, OPN was increased in A\u03b2(+) positron emission tomography (PET) and tau(+) PET individuals, and associated with an accelerated rate of conversion to AD. OPN was elevated in autopsy\u2010confirmed AD brains.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Strong associations between CSF OPN and key markers of AD pathophysiology suggest a significant role for OPN in tau neurobiology, particularly in the early stages of the disease.<\/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>In the Pre\u2010symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease cohort, we discovered that cerebrospinal fluid (CSF) osteopontin (OPN) levels can indicate early synaptic dysfunction, tau deposition, and neuronal loss in cognitively unimpaired elderly with a parental history.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>CSF OPN is elevated in amyloid beta(+) positron emission tomography (PET) and tau(+) PET individuals.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Elevated CSF OPN is associated with an accelerated rate of conversion to Alzheimer's disease (AD).<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Elevated CSF OPN is associated with an accelerated rate of cognitive decline on the Alzheimer's Disease Assessment Scale\u2010Cognitive subscale 13, Montreal Cognitive Assessment, Mini\u2010Mental State Examination, and Clinical Dementia Rating Scale Sum of Boxes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>OPN mRNA and protein levels are significantly upregulated in the frontal cortex of autopsy\u2010confirmed AD brains.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.14065","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:19:03Z","timestamp":1722212343000},"page":"6008-6031","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Osteopontin: A novel marker of pre\u2010symptomatic sporadic Alzheimer's disease"],"prefix":"10.1002","volume":"20","author":[{"given":"Marc James","family":"Quesnel","sequence":"first","affiliation":[{"name":"McGill University  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Douglas Mental Health University Institute  Verdun Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Labont\u00e9","sequence":"additional","affiliation":[{"name":"Douglas Mental Health University Institute  Verdun Qu\u00e9bec Canada"},{"name":"Centre for the Studies in the Prevention of Alzheimer's Disease Douglas Mental Health University Institute  Verdun Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Picard","sequence":"additional","affiliation":[{"name":"Douglas Mental Health University Institute  Verdun Qu\u00e9bec Canada"},{"name":"Centre for the Studies in the Prevention of Alzheimer's Disease Douglas Mental Health University Institute  Verdun Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Bowie","sequence":"additional","affiliation":[{"name":"McGill University  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Douglas Mental Health University Institute  Verdun Qu\u00e9bec Canada"}],"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, University of Gothenburg, SU\/Sahlgrenska  Gothenburg Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital, SU\/M\u00f6lndals sjukhus  M\u00f6lndal Sweden"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology  Queen Square London UK"},{"name":"UK Dementia Research Institute at UCL  London UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park  Shatin, N.T. 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