Network-based analyses identify GFAP as a cross-domain hub linking synaptic, neuronal, and inflammatory markers in Alzheimer’s disease

This study highlights GFAP as a key marker in Alzheimer's disease, linking various pathological processes, but does not establish direct causation.

Summary and findings

This study measured cerebrospinal fluid (CSF) biomarkers in 60 Alzheimer's disease (AD) patients and 40 healthy controls (HC). It found that AD patients had significantly higher CSF levels of neurogranin, SNAP-25, CAP2, NfL, GFAP, IL-1β, and TNF-α compared to controls. The analysis identified GFAP as a central hub linking various pathological markers in AD.

Abstract

<title>Abstract</title> <p>Alzheimer’s disease (AD) is characterized by complex alterations in synaptic, glial, neuronal and inflammatory markers. Given its emerging role at the interface of synaptic dysfunction and inflammation, the astrocytic marker GFAP may represent a cross-domain hub linking synaptic, neuronal and inflammatory alterations. Using multivariate and network-based analyses we examined the relationships among cerebrospinal fluid (CSF) biomarkers of astrocytic activation and synaptic failure, inflammation, and neurodegeneration in biologically confirmed AD patients and healthy controls (HC). We studied 60 AD patients and 40 HC. CSF concentrations of neurogranin, SNAP-25, CAP2, NfL, GFAP, IL-1α, IL-1β, IL-8, MCP-1, TNF-α were measured. Associations were assessed using Spearman correlations, LASSO regression, and network analysis to characterize multivariate dependency structures. Compared with controls, AD patients showed significantly higher CSF levels of neurogranin, SNAP-25, CAP2, NfL, GFAP, IL-1β, TNF-α. In AD, synaptic biomarkers were strongly intercorrelated and associated with astroglial activation, inflammatory markers, and tau-related pathology. Network analysis identified GFAP as a cross-domain hub linking synaptic, inflammatory, and neurodegenerative domains in AD. In controls, GFAP was mainly associated with neuronal injury markers. Network-based modelling revealed a disease-related reorganization of biomarker connectivity in AD, with GFAP occupying a central cross-domain position, supporting a systems-level view of AD pathophysiology.</p>

Key findings

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Limitations

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