Exploring biomarkers of neurodegeneration in epilepsy: Critical insights

The advent of biofluid biomarkers for neurodegenerative disorders has precipitated a surge in recent evidence regarding their role in epilepsy. In this literature review, we examine the diagnostic, prognostic, and therapeutic potential of several biomarkers, including amyloid-beta (Aβ) protein, total (t-tau), phosphorylated tau (p-tau) protein, alpha-synuclein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and others in epilepsy. Recent studies highlight mid-life Aβ levels as a risk factor for late-onset epilepsy. Several studies also show that amyloid pathology correlates with cognitive impairment in people with epilepsy (PWE). T-tau and p-tau levels in CSF and serum show diagnostic potential, particularly for temporal lobe epilepsy (TLE). Tau may also have significant prognostic utility in cognition of PWE and status epilepticus. Despite promising findings, larger prospective studies are needed to validate these biomarkers for routine clinical use in older PWE. Mouse models demonstrate tau's association with increased seizure susceptibility and mortality and the association of tau reduction with reduced seizure severity. This further highlights the need to investigate tau-targeting therapies in future studies in older PWE. Recent small-scale retrospective studies link NfL's role in cognitive impairment and status epilepticus, suggest a prognostic role of alpha-synuclein in certain epilepsies, and propose emerging diagnostic and prognostic roles of other biomarkers in epilepsy, including GFAP, cytoskeletal proteins, and S100B. However, larger longitudinal studies are needed to confirm these findings. We propose integrating some of these biomarkers into clinical practice for selected older adults with epilepsy. This integration could improve diagnostic accuracy, prognosticate outcomes, and identify therapeutic targets that may improve seizure control and mitigate the progression of cognitive decline in PWE.