{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:02:12Z","timestamp":1790085732632,"version":"4.0.1"},"reference-count":32,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"712","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,9,6]]},"abstract":"<jats:p>\n            Alzheimer\u2019s disease (AD) is a neurodegenerative disease with heterogenous pathophysiological changes that develop years before the onset of clinical symptoms. These preclinical changes have generated considerable interest in identifying markers for the pathophysiological mechanisms linked to AD and AD-related disorders (ADRD). On the basis of our prior work integrating cerebrospinal fluid (CSF) and brain proteome networks, we developed a reliable and high-throughput mass spectrometry\u2013selected reaction monitoring assay that targets 48 key proteins altered in CSF. To test the diagnostic utility of these proteins and compare them with existing AD biomarkers, CSF collected at baseline visits was assayed from 706 participants recruited from the Alzheimer\u2019s Disease Neuroimaging Initiative. We found that the targeted CSF panel of 48 proteins (CSF 48 panel) performed at least as well as existing AD CSF biomarkers (A\u03b2\n            <jats:sub>42<\/jats:sub>\n            , tTau, and pTau\n            <jats:sub>181<\/jats:sub>\n            ) for predicting clinical diagnosis, FDG PET, hippocampal volume, and measures of cognitive and dementia severity. In addition, for each of those outcomes, the CSF 48 panel plus the existing AD CSF biomarkers significantly improved diagnostic performance. Furthermore, the CSF 48 panel plus existing AD CSF biomarkers significantly improved predictions for changes in FDG PET, hippocampal volume, and measures of cognitive decline and dementia severity compared with either measure alone. A potential reason for these improvements is that the CSF 48 panel reflects a range of altered biology observed in AD\/ADRD. In conclusion, we show that the CSF 48 panel complements existing AD CSF biomarkers to improve diagnosis and predict future cognitive decline and dementia severity.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adg4122","type":"journal-article","created":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T17:58:41Z","timestamp":1694023121000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":65,"title":["A protein panel in cerebrospinal fluid for diagnostic and predictive assessment of Alzheimer\u2019s disease"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0489-9167","authenticated-orcid":true,"given":"Rafi","family":"Haque","sequence":"first","affiliation":[{"name":"Goizueta Alzheimer\u2019s Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6574-0833","authenticated-orcid":true,"given":"Caroline M.","family":"Watson","sequence":"additional","affiliation":[{"name":"Goizueta Alzheimer\u2019s Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3480-3234","authenticated-orcid":true,"given":"Jiaqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5083-0614","authenticated-orcid":true,"given":"E. Kathleen","family":"Carter","sequence":"additional","affiliation":[{"name":"Goizueta Alzheimer\u2019s Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5880-1888","authenticated-orcid":true,"given":"Duc M.","family":"Duong","sequence":"additional","affiliation":[{"name":"Goizueta Alzheimer\u2019s Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8810-620X","authenticated-orcid":true,"given":"James J.","family":"Lah","sequence":"additional","affiliation":[{"name":"Goizueta Alzheimer\u2019s Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6360-6726","authenticated-orcid":true,"given":"Aliza P.","family":"Wingo","sequence":"additional","affiliation":[{"name":"Division of Mental Health Atlanta VA Medical Center, Decatur, GA 30033, USA."},{"name":"Department of Psychiatry, Emory University School of Medicine, Atlanta, GA 30329, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5466-0053","authenticated-orcid":true,"given":"Blaine R.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Goizueta Alzheimer\u2019s Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0604-2944","authenticated-orcid":true,"given":"Erik C. B.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Goizueta Alzheimer\u2019s Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1376-8532","authenticated-orcid":true,"given":"Andrew J.","family":"Saykin","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46204, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7650-1210","authenticated-orcid":true,"given":"Leslie M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA."},{"name":"Center for Neurodegenerative Disease Research, University of Pennsylvania, Philadelphia, PA 19104, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8694-9211","authenticated-orcid":true,"given":"Nicholas T.","family":"Seyfried","sequence":"additional","affiliation":[{"name":"Goizueta Alzheimer\u2019s Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7679-6282","authenticated-orcid":true,"given":"Thomas S.","family":"Wingo","sequence":"additional","affiliation":[{"name":"Goizueta Alzheimer\u2019s Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3153-502X","authenticated-orcid":true,"given":"Allan I.","family":"Levey","sequence":"additional","affiliation":[{"name":"Goizueta Alzheimer\u2019s Disease Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA."},{"name":"Department of Neurology, Emory University School of Medicine, Atlanta, GA 30329, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2018.02.018"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006189"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-006-0127-z"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e318232a379"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00520-w"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000219668.47116.e6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.11.1087"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.04.002"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00999-y"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0815-6"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0154-9"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb5398"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2016.11.006"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09613-z"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0635-5"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz9360"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-023-02158-3"},{"key":"e_1_3_2_19_2","first-page":"152","article-title":"14-3-3 proteins in neurological disorders","volume":"3","author":"Foote M.","year":"2012","unstructured":"M. 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