Journal Article

DZNE-2025-01337

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Age-Specific Control and Alzheimer Disease Reference Curves and z-Scores for Glial Fibrillary Acidic Protein in Blood.

Halbgebauer, S. (First author)DZNE* ; Fazeli, B. ; Klose, V.DZNE* ; Nagel, G. ; Rosenbohm, A. ; Rothenbacher, D. ; Bachhuber, F. ; Jesse, S.Extern* ; Otto, M. ; Landwehrmeyer, G. B.Extern* ; Abdelhak, A. ; Petzold, A. ; Ludolph, A. C.DZNE* ; Tumani, H.Extern*

2025
American Association for Clinical Chemistry Washington, DC

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Please use a persistent id in citations: doi:10.1093/clinchem/hvaf120

Abstract: Serum glial fibrillary acidic protein (GFAP) is a biomarker for astrocytic injury and astrogliosis. Concentrations are elevated in numerous neurological disorders, including a pronounced increase in Alzheimer disease (AD). However, GFAP levels in the serum also increase with age. Consequently, the integration of GFAP levels into clinical routine and their interpretation demands age-adjusted reference values.Serum from 1273 subjects (952 noninflammatory and nonneurodegenerative neurological controls and 321 subjects with AD) was analyzed for GFAP using the microfluidic Ella system. Age-dependent serum GFAP reference values were estimated by additive quantile regression analysis and visualized with percentiles and z-scores.AD exhibited elevated serum GFAP levels in comparison to control patients (P < 0.0001). This remained the case when the newly generated age-corrected z-scores were applied (P < 0.0001). In the control cohort, a nonlinear elevation of serum GFAP with increasing age was observed (Spearman correlation coefficient 0.62, 95% CI 0.58-0.66, P < 0.0001). In contrast, the AD cohort exhibited a more linear increase (0.16, 95% CI 0.05-0.26, P = 0.004). Age-dependent cut-offs for serum GFAP were determined for different AD age groups. The calculated areas under the curve (AUCs; 0.97) demonstrated excellent diagnostic test performance in the early-onset age group. This effect was less marked in the elderly subjects (AUC 0.72).Our novel GFAP z-scores enable the integration and interpretation of serum GFAP levels in clinical practice, moving from the group to individual level. They support both intra- and interindividual interpretation of single GFAP levels in neurological diseases with astrocytic pathology, including an accurate discrimination of AD.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: blood (MeSH) ; Alzheimer Disease: diagnosis (MeSH) ; Glial Fibrillary Acidic Protein: blood (MeSH) ; Aged (MeSH) ; Male (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; Reference Values (MeSH) ; Biomarkers: blood (MeSH) ; Aged, 80 and over (MeSH) ; Age Factors (MeSH) ; Adult (MeSH) ; Case-Control Studies (MeSH) ; Glial Fibrillary Acidic Protein ; Biomarkers ; GFAP protein, human

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Contributing Institute(s):

1. Clinical Study Center (Ulm) (Clinical Study Center (Ulm))
2. Neuroepidemiology (AG Zhan)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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