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However, their relative prognostic and monitoring capabilities for cognitive decline, amyloid-\u03b2 (A\u03b2) accumulation and grey matter loss in cognitively unimpaired elderly require further investigation over extended time periods.<\/jats:p>\n               <jats:p>This prospective cohort study in cognitively unimpaired elderly [n = 185, mean age (range) = 69 (53\u201384) years, 48% female] examined the prognostic and monitoring capabilities of glial fibrillary acidic protein (GFAP), neurofilament light (NfL), A\u03b21-42\/A\u03b21-40 and phosphorylated tau (pTau)181 through their quantification in serum. All participants underwent baseline A\u03b2-PET, MRI and blood sampling as well as 2-yearly cognitive testing. A subset additionally underwent A\u03b2-PET (n = 109), MRI (n = 106) and blood sampling (n = 110) during follow-up [median time interval (range) = 6.1 (1.3\u201311.0) years]. Matching plasma measurements were available for A\u03b21-42\/A\u03b21-40 and pTau181 (both n = 140).<\/jats:p>\n               <jats:p>Linear mixed-effects models showed that high serum GFAP and NfL predicted future cognitive decline in memory (\u03b2GFAP\u00d7Time = \u22120.021, PFDR = 0.007 and \u03b2NfL\u00d7Time = \u22120.031, PFDR = 0.002) and language (\u03b2GFAP\u00d7Time = \u22120.021, PFDR = 0.002 and \u03b2NfL\u00d7Time = \u22120.018, PFDR = 0.03) domains. Low serum A\u03b21-42\/A\u03b21-40 equally but independently predicted memory decline (\u03b2A\u03b21-42\/A\u03b21-40\u00d7Time = \u22120.024, PFDR = 0.02). Whole-brain voxelwise analyses revealed that low A\u03b21-42\/A\u03b21-40 predicted A\u03b2 accumulation within the precuneus and frontal regions, high GFAP and NfL predicted grey matter loss within hippocampal regions and low A\u03b21-42\/A\u03b21-40 predicted grey matter loss in lateral temporal regions. Serum GFAP, NfL and pTau181 increased over time, while A\u03b21-42\/A\u03b21-40 decreased only in A\u03b2-PET-negative elderly. NfL increases associated with declining memory (\u03b2NfLchange\u00d7Time = \u22120.030, PFDR = 0.006) and language (\u03b2NfLchange\u00d7Time = \u22120.021, PFDR = 0.02) function and serum A\u03b21-42\/A\u03b21-40 decreases associated with declining language function (\u03b2A\u03b21-42\/A\u03b21-40\u00d7Time = \u22120.020, PFDR = 0.04). GFAP increases associated with A\u03b2 accumulation within the precuneus and NfL increases associated with grey matter loss. Baseline and longitudinal serum pTau181 only associated with A\u03b2 accumulation in restricted occipital regions. In head-to-head comparisons, serum outperformed plasma A\u03b21-42\/A\u03b21-40 (\u0394AUC = 0.10, PDeLong, FDR = 0.04), while both plasma and serum pTau181 demonstrated poor performance to detect asymptomatic A\u03b2-PET positivity (AUC = 0.55 and 0.63, respectively). However, when measured with a more phospho-specific assay, plasma pTau181 detected A\u03b2-positivity with high performance (AUC = 0.82, PDeLong, FDR &amp;lt; 0.007).<\/jats:p>\n               <jats:p>In conclusion, serum GFAP, NfL and A\u03b21-42\/A\u03b21-40 are valuable prognostic and\/or monitoring tools in asymptomatic stages providing complementary information in a time- and pathology-dependent manner.<\/jats:p>","DOI":"10.1093\/brain\/awad330","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T11:09:12Z","timestamp":1696331352000},"page":"936-948","source":"Crossref","is-referenced-by-count":43,"title":["Longitudinal associations of serum biomarkers with early cognitive, amyloid and grey matter changes"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6729-7601","authenticated-orcid":false,"given":"Steffi","family":"De Meyer","sequence":"first","affiliation":[{"name":"Laboratory for Molecular Neurobiomarker Research, Department of Neurosciences, KU Leuven , 3000 Leuven , Belgium"},{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven , 3000 Leuven , Belgium"},{"name":"Alzheimer Research Centre, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena R","family":"Blujdea","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Amsterdam UMC , 1081 HZ Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolien","family":"Schaeverbeke","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven , 3000 Leuven , Belgium"},{"name":"Alzheimer Research Centre, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7964-7963","authenticated-orcid":false,"given":"Mariska","family":"Reinartz","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven , 3000 Leuven , Belgium"},{"name":"Alzheimer Research Centre, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1777-4742","authenticated-orcid":false,"given":"Emma S","family":"Luckett","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven , 3000 Leuven , Belgium"},{"name":"Alzheimer Research Centre, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven , 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3000 Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4061-0837","authenticated-orcid":false,"given":"Charlotte E","family":"Teunissen","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Amsterdam UMC , 1081 HZ Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6237-2502","authenticated-orcid":false,"given":"Rik","family":"Vandenberghe","sequence":"additional","affiliation":[{"name":"Laboratory for Cognitive Neurology, Department of Neurosciences, KU Leuven , 3000 Leuven , Belgium"},{"name":"Alzheimer Research Centre, Leuven Brain Institute (LBI), KU Leuven , 3000 Leuven , Belgium"},{"name":"Department of Neurology, UZ Leuven , 3000 Leuven , 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