Plasma GFAP outperforms CSF GFAP in detecting amyloid pathology and is associated with increased risk of clinical progression in early Alzheimer’s disease

Cetindag, Arda C. ; Schipke, Carola G.; Esselmann, Hermann ; Kruse, Niels; Wiltfang, Jens ; Schneider, Anja ; Fliessbach, Klaus ; Miklitz, Carolin ; Maier, Franziska ; Buerger, Katharina ; Janowitz, Daniel ; Ewers, Michael ; Stöcklein, Sophia ; Perneczky, Robert ; Rauchmann, Boris-Stephan ; Kurz, Carolin ; Teipel, Stefan ; Kilimann, Ingo ; Goerss, Doreen ; Laske, Christoph ; Sodenkamp, Sebastian ; Najafpour, Elham; Wagner, Michael ; Roeske, Sandra ; Frommann, Ingo ; Stark, Melina ; Brosseron, Frederic ; Ramirez, Alfredo ; Kleineidam, Luca ; Priller, Josef ; Spruth, Eike Jakob ; Gemenetzi, Maria; Altenstein, Slawek ; Düzel, Emrah ; Glanz, Wenzel ; Incesoy, Enise I. ; Butryn, Michaela; Bauer, Chris; Jessen, Frank und Peters, Oliver (2026): Plasma GFAP outperforms CSF GFAP in detecting amyloid pathology and is associated with increased risk of clinical progression in early Alzheimer’s disease. In: Journal of Prevention of Alzheimer's Disease, Vol. 13, No. 5, 100544

Abstract

Background: Early and accurate detection of Alzheimer’s disease (AD) is essential for timely intervention and development of disease-modifying treatments. The DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) provides a deeply phenotyped cohort covering preclinical and early clinical stages, including subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Astrocyte reactivity and its biomarkers, particularly glial fibrillary acidic protein (GFAP), have gained increasing attention in AD research; however, the relationship between GFAP and amyloid in early disease, as well as its potential prognostic value beyond its association with amyloid status, remains insufficiently understood.

Objectives: To evaluate the performance of CSF and plasma GFAP across early disease stages, compare these measures according to amyloid status, and assess the prognostic value of GFAP for clinical progression across diagnostic stages during longitudinal follow-up.

Setting: This study used data from the multicenter DELCODE cohort in Germany, including participants with available plasma and/or CSF samples and standardized clinical, cognitive, imaging, and biomarker assessments.

Measurements: GFAP concentrations in plasma and CSF were quantified using validated immunoassay platforms. Standard CSF AD biomarkers and ApoE genotype were measured using established assays. Amyloid status was defined by the CSF Aβ42/40 ratio. Longitudinal follow-up occurred annually for up to ~10 years, with clinical conversion determined according to NIA-AA criteria.

Results: Plasma and CSF GFAP increased across the AD continuum, with higher levels in MCI and AD (p < 0.001). Plasma GFAP showed a stronger association with amyloid status than CSF GFAP across all groups. In MCI, plasma GFAP combined with age and ApoE4 yielded an AUC of 0.87. Elevated plasma GFAP predicted increased risk of conversion to MCI (HR = 2.19, p < 0.001; adjusted HR = 1.70, p = 0.0056) and AD dementia (HR = 3.5; adjusted HR = 2.49 both p < 0.001).

Conclusion: Plasma GFAP is a sensitive, minimally invasive biomarker with diagnostic relevance for amyloid detection and prognostic relevance for clinical progression in early AD.

• Item Type: Journal article
• Faculties: Medicine > Munich Cluster for Systems Neurology (SyNergy); Medicine > Institute for Stroke and Dementia Research (ISD); Medicine > Institute for Diagnostic and Interventional Neuroradiology; Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Psychiatry and Psychotherapy; Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Radiology
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 2274-5807
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198