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Atypical White Matter Hyperintensities Markedly Impact Plasma Neurofilament Light Chain Variability in GRN Patients
Joana Vítor1, Dario Saracino1,2, Sebastian Ströer3
1Sorbonne Université, Paris Brain Institute, Institut du Cerveau, ICM, Inserm U1127, CNRS UMR 7225, APHP, Hôpital Pitié-Salpêtrière, Paris, France.
Abstract:
GRN mutations, causing frontotemporal dementia, can be associated with atypical white matter hyperintensities (WMH). We hypothesized that the presence of WMH may impact neurofilament light chain (NfL) levels, markers of neuroaxonal damage. We analyzed plasma NfL in 20 GRN patients and studied their association to visually-scored WMH burden. The 12 patients displaying atypical WMH had significantly higher NfL levels (98.4±34.9 pg/mL) than those without WMH (47.2±29.4 pg/mL, p = 0.003), independently from age, disease duration and Fazekas-Schmidt grade. NfL correlated with WMH burden (rho = 0.55, p = 0.01). This study prompts considering WMH burden as a variability factor when evaluating NfL levels in GRN patients.
Insights
Genetic mutations in GRN, linked to frontotemporal dementia, are associated with white matter hyperintensities (WMH). Higher WMH burden correlates with increased neurofilament light chain (NfL) levels, indicating neuroaxonal damage.
Area of Science:
- Neuroscience
- Genetics
- Neurology
Background:
- GRN gene mutations are a known cause of frontotemporal dementia (FTD).
- FTD can present with atypical white matter hyperintensities (WMH) on neuroimaging.
- Neurofilament light chain (NfL) is a biomarker for neuroaxonal damage.
Purpose of the Study:
- To investigate the relationship between WMH burden and plasma NfL levels in patients with GRN mutations.
- To determine if WMH influences NfL levels, a marker of neuroaxonal damage.
Main Methods:
- Analysis of plasma NfL levels in 20 patients with GRN mutations.
- Visual scoring of WMH burden in study participants.
- Statistical analysis to assess the association between WMH and NfL, controlling for clinical factors.
Main Results:
- Patients with atypical WMH showed significantly higher NfL levels (98.4±34.9 pg/mL) compared to those without WMH (47.2±29.4 pg/mL, p=0.003).
- NfL levels positively correlated with WMH burden (rho=0.55, p=0.01).
- This association remained significant independently of age, disease duration, and Fazekas-Schmidt grade.
Conclusions:
- WMH burden is a significant factor influencing NfL levels in GRN mutation carriers.
- Consideration of WMH is crucial for interpreting NfL levels in the context of GRN-associated FTD.
- Findings highlight WMH as a potential contributor to neuroaxonal damage variability in this patient group.
