Atypical White Matter Hyperintensities Markedly Impact Plasma Neurofilament Light Chain Variability in GRN Patients

Article type: Short Communication

Authors: Vítor, Joana^a | Saracino, Dario^{a; b} | Ströer, Sebastian^c | Camuzat, Agnès^a | Dorgham, Karim^d | Clot, Fabienne^e | Martin-Hardy, Philippe^a | Pasquier, Florence^f | The French research network on FTLD/FTLD-ALS, Predict-PGRN study group | Le Ber, Isabelle^{a; b; *}

Affiliations: [a] Sorbonne Université, Paris Brain Institute, Institut du Cerveau, ICM, Inserm U1127, CNRS UMR 7225, APHP, Hôpital Pitié-Salpêtrière, Paris, France | [b] AP-HP, Reference Centre for Rare or Early onset Dementias, IM2A, Department of Neurology, Hôpital Pitié-Salpêtrière, Paris, France | [c] Department of Neuroradiology, Pitié-Salpêtrière Hospital, AP-HP, Paris, France | [d] Sorbonne Université, INSERM, Centred’Immunologie et des Maladies Infectieuses-Paris (CIMI-Paris), Paris, France | [e] AP-HP.Sorbonne Université, Department of Genetics, UF of Molecular and Cellular Neurogenetics, Hôpital Pitié-Salpêtrière, Paris, France | [f] Univ Lille, Inserm 1172 LilNCOG, CHU Lille, CNR-MAJ, DistAlz, LiCEND Lille, France

Correspondence: [*] Correspondence to: Dr. Isabelle Le Ber, MD, PhD, Sorbonne Université, Paris Brain Institute, Institut du Cerveau (ICM), Inserm U1127, CNRS UMR 7225; Reference Centre for Rare or Early Dementias, IM2A, Department of Neurology, Hôpital Universitaire Pitié-Salpêtrière, 47-83 boulevard de l’Hôpital, 75013 Paris, France. E-mail:isabelle.leber@upmc.fr.

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.

Keywords: Amyotrophic lateral sclerosis, frontotemporal dementia, frontotemporal lobar degeneration, GRN , leukopathy, neurofilament light chain, progranulin, white matter hyperintensities

DOI: 10.3233/JAD-230315

Journal: Journal of Alzheimer's Disease, vol. 94, no. 4, pp. 1351-1360, 2023