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

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.