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Dementia and geriatric cognitive disorders
Published

Limited Diagnostic Performance of Cerebrospinal Fluid Glial Fibrillary Acidic Protein in Dementia

Authors

Pontus Erickson, Tobias Borgh Skillbäck, Silke Kern, Ingmar Skoog, Linus Jönsson, Ulf Andreasson, Kaj Blennow, Maria Eriksdotter, Henrik Zetterberg

Abstract

Dement Geriatr Cogn Disord. 2026 Jan 20:1-9. doi: 10.1159/000550601. Online ahead of print.

ABSTRACT

INTRODUCTION: Cerebrospinal fluid (CSF) glial fibrillary acidic protein (GFAP) is a neuroinflammatory marker reflecting reactive astrogliosis and is measured regularly in clinical practice. However, its diagnostic utility in differentiating dementia subtypes remains unclear. This study aimed to evaluate differences in CSF GFAP concentrations and its associations with markers of disease severity and amyloid pathology.

METHODS: We conducted a retrospective cohort study using three datasets encompassing a broad range of dementia diagnoses. Included variables were CSF GFAP, β-amyloid 42 (Aβ42), the Aβ42/Aβ40 ratio, Mini-Mental State Examination (MMSE) scores, and time from sampling to death.

RESULTS: A total of 1,345 individuals were included. In Parkinson's disease dementia (PDD) and Lewy body dementia, GFAP levels were similar (p > 0.05). Lower levels were observed in PDD compared to early-onset Alzheimer's disease (EAD), late-onset AD (LAD), and vascular dementia (VaD) (all p < 0.05); however, the discriminative performance was low-to-moderate: PDD versus LAD (AUROC = 0.74, CI = 0.64-0.84, p < 0.001), VaD (AUROC = 0.71, CI =0.61-0.81, p < 0.001) and EAD (AUROC = 0.59, CI = 0.47-0.71, p = 0.13). Associations were seen with MMSE in mixed AD and VaD (p = 0.027), but not in the other diagnostic categories. GFAP levels did not differ between subjects grouped according to Aβ42/Aβ40 status (p > 0.05).

CONCLUSION: CSF GFAP did not exhibit clinically relevant diagnostic or prognostic value in dementia. Further studies are needed to clarify its role in PDD.

PMID:41557565 | DOI:10.1159/000550601

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg