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However, plasma GFAP has not been investigated in cognitively normal older adults at risk of AD, based on brain amyloid-\u03b2 (A\u03b2) load. Cross-sectional analyses were carried out for plasma GFAP and plasma A\u03b21\u201342\/A\u03b21\u201340 ratio, a blood-based marker associated with brain A\u03b2 load, in participants (65\u201390 years) categorised into low (A\u03b2\u2212,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200963) and high (A\u03b2+,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200933) brain A\u03b2 load groups via A\u03b2 positron emission tomography. Plasma GFAP, A\u03b21\u201342, and A\u03b21\u201340 were measured using the Single molecule array (Simoa) platform. Plasma GFAP levels were significantly higher (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.00001), and plasma A\u03b21\u201342\/A\u03b21\u201340 ratios were significantly lower (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.005), in A\u03b2+ participants compared to A\u03b2\u2212 participants, adjusted for covariates age, sex, and apolipoprotein E-\u03b54 carriage. A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished A\u03b2+ from A\u03b2\u2212 (area under the curve, AUC\u2009=\u20090.78), but was outperformed when plasma GFAP was added to the base model (AUC\u2009=\u20090.91) and further improved with plasma A\u03b21\u201342\/A\u03b21\u201340 ratio (AUC\u2009=\u20090.92). The current findings demonstrate that plasma GFAP levels are elevated in cognitively normal older adults at risk of AD. These observations suggest that astrocytic damage or activation begins from the pre-symptomatic stage of AD and is associated with brain A\u03b2 load. Observations from the present study highlight the potential of plasma GFAP to contribute to a diagnostic blood biomarker panel (along with plasma A\u03b21\u201342\/A\u03b21\u201340 ratios) for cognitively normal older adults at risk of AD.\n                  <\/jats:p>","DOI":"10.1038\/s41398-020-01137-1","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T09:27:20Z","timestamp":1610357240000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":419,"title":["Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer\u2019s disease"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4877-1958","authenticated-orcid":false,"given":"Pratishtha","family":"Chatterjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Pedrini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Stoops","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3573-1554","authenticated-orcid":false,"given":"Kathryn","family":"Goozee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor L.","family":"Villemagne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prita R.","family":"Asih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0341-7445","authenticated-orcid":false,"given":"Inge M. 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HRS has received ruminations for working with Pfizer and Takeda. H.Z. has served at scientific advisory boards for Denali, Roche Diagnostics, Wave, Samumed, Siemens Healthineers, Pinteon Therapeutics, and CogRx, has given lectures in symposia sponsored by Fujirebio, Alzecure, and Biogen, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). K.B. has served as a consultant, at advisory boards, or at data monitoring committees for Abcam, Axon, Biogen, JOMDD\/Shimadzu. Julius Clinical, Lilly, MagQu, Novartis, Roche Diagnostics, and Siemens Healthineers, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. H.M.V. is a co-founder of ADx NeuroSciences and a founder of Biomarkable. All other authors report no conflict of interest in relation to the current study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"27"}}