The Role of Neurodegenerative and Dementia Biomarkers in Epilepsy
Abstract number :
2.064
Submission category :
14. Neuropathology of Epilepsy
Year :
2024
Submission ID :
823
Source :
www.aesnet.org
Presentation date :
12/8/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Rida Farhan, MD – Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
Syeda Amrah Hashmi, MD – University of Virginia School of Medicine, Charlottesville, VA
Jaideep Kapur, MBBS, PhD – University of Virginia
Anelyssa D’Abreu, MD, PhD, MPH – University of Virginia School of Medicine, Charlottesville, VA
Vineet Punia, MD – Cleveland Clinic
Carol Manning, MD – University of Virginia
Ifrah Zawar, MD, MS-CR – University of Virginia
Rationale: With the availability of biofluid biomarkers for neurodegenerative disorders, there has been a surge in recent evidence about their role in epilepsy. In this review, we address the potential diagnostic, prognostic, and therapeutic significance of amyloid-beta (Aβ) protein, total (T-tau), phosphorylated tau (p-tau) protein, alpha-synuclein (αS), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and other biomarkers in epilepsy.
Methods: We conducted a literature review using the following search strategy: (epilep*[Title/Abstract]) AND (amyloid [Title/Abstract] OR tau [Title/Abstract] OR synuclein [Title/Abstract] OR NfL [Title/Abstract] OR GFAP [Title/Abstract]). The search was performed on PubMed till December 2023. 1774 results were screened, 90 were shortlisted and 64 articles were included. Relevant data was extracted from selected articles and carefully analyzed.
Results: Of the 64 articles, 9 (14%) were on Aβ, 21 (33%) were on tau, 17 (27%) were on both Aβ and tau, 3 (5%) were on αS, 5 (8%) were on NfL, while 9 (14%) on GFAP and other biomarkers. For Aβ, the most common manifestation was a decrease in the cerebrospinal fluid (CSF) levels and increased deposits in the cortex of people with epilepsy (PWE). These studies suggest that mid-life Aβ levels have an association with the development of late-onset epilepsy, and amyloid pathology correlates with cognitive impairment in PWE. In the absence of neurodegeneration in a mouse model, Aβ was implicated in network dysfunction on EEG which was prevented by reducing tau levels. The majority of the studies were conducted on the role of tau in epilepsy, demonstrating 37-38% of cases to have a substantial tau accumulation. T-tau levels were commonly increased in CSF, while p-tau was increased in brain tissue, especially the hippocampus. T-tau and p-tau levels in CSF and serum appear to have diagnostic utility in epilepsy, especially temporal lobe epilepsy. Tau may also have significant prognostic utility in cognition of PWE and status epilepticus (SE). Animal studies found tau's association with increased seizure susceptibility and mortality and reduced seizure severity with tau reduction. Future studies need to investigate tau-targeting therapies in older PWE. αS showed an increase in CSF and serum levels, particularly in drug-resistant and pediatric epilepsy. Small-scale retrospective studies highlight NfL's correlation with cognitive impairment and SE, the potential prognostic role of αS in certain epilepsies, and emerging diagnostic and prognostic roles of GFAP, cytoskeletal proteins, and S100B in epilepsy. However, there is a need for larger longitudinal studies to confirm these findings and incorporate these biomarkers in routine clinical practice.
Conclusions: We highlight the need to consider using some of these biomarkers in clinical practice in selected older adults with epilepsy. In addition to their diagnostic and prognostic utility, identifying therapeutic targets may improve seizure control and mitigate the progression of cognitive decline in PWE.
Funding: Alzheimer's Association, American Epilepsy Society, NIH
Neuropathology of Epilepsy