Cerebrospinal Fluid and Plasma Biomarkers do not Differ in the Presenile and Late-Onset Behavioral Variants of Frontotemporal Dementia

Article type: Research Article

Authors: Marelli, Cecilia^{a; b; *} | Hourregue, Claire^{a; 1} | Gutierrez, Laure-Anne^{a; c} | Paquet, Claire^d | Menjot de Champfleur, Nicolas^{e; f; g} | De Verbizier, Delphine^h | Jacob, Melissa^a | Dubois, Jonathan^c | Maleska, Aleksandra Maceskiⁱ | Hirtz, Christopheⁱ | Navucet, Sophie^a | Bennys, Karim^a | Dumurgier, Julien^d | Cognat, Emmanuel^d | Berr, Claudine^{a; c} | Magnin, Eloi^j | Lehmann, Sylvainⁱ | Gabelle, Audrey^{a; c}

Affiliations: [a] Memory Research and Resources Alzheimer Center, Department of Neurology, University Hospital Center, Gui de Chauliac Hospital, Montpellier, France | [b] Inserm U1198 MMDN, Montpellier, France; EPHE, Paris, France, Montpellier, France | [c] INSERM U1061, Univ Montpellier, Neuropsychiatry: Epidemiological and Clinical Research, Montpellier, France | [d] Center of Cognitive Neurology, Lariboisière Fernand-Widal Hospital, APHP, University of Paris Diderot, Paris, France | [e] Institut d’Imagerie Fonctionnelle Humaine, I2FH, University Hospital Center, Gui de Chauliac Hospital, Montpellier, France | [f] Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier, France | [g] Team “Plasticity of Central Nervous System, Stem Cells and Glial Tumors, ” Institut National de la Santé et de la Recherche Médicale Unité 583, Institut of Neurosciences of Montpellier, Saint Eloi Hospital, Montpellier, France | [h] Department of Nuclear Medicine, University Hospital Center, Gui de Chauliac Hospital, Montpellier, France | [i] Laboratoire de Biochimie Protéomique Clinique, INSERM-UM 1183, University Hospital Center, University of Montpellier, Montpellier, France | [j] Department of Neurology, Centre Mémoire Ressources Recherche Besançon Franche-Comté, CHU de Besançon, Besançon, France

Correspondence: [*] Correspondence to: Dr. Cecilia Marelli, Department of Neurology and Memory Clinic, University Hospital Center, Gui de Chauliac Hospital, Montpellier, France. Tel.: +33 0467336029; Fax: 04673306036; E-mail: [email protected].

Note: [†] Current address: Center of Cognitive Neurology, Lariboisière Fernand-Widal Hospital, APHP, University Paris Diderot, Paris, France

Abstract: Background:Memory troubles and hippocampal atrophy are considered more frequent and focal atrophy less severe in late-onset (>65 years) than in presenile behavioral variant of frontotemporal dementia (bvFTD). Objective:To compare cerebrospinal fluid (CSF) and plasma biomarkers in late-onset and presenile bvFTD. Methods:Multicentric retrospective study (2007-2017) on patients with clinical diagnosis of bvFTD. Results:This study included 44 patients (67%) with presenile and 22 (33%) with late-onset bvFTD (comparable mean disease duration; n = 11 with causal mutations). Hippocampal atrophy was more frequent (80% versus 25.8%) and severe in late-onset bvFTD (median Scheltens score: 3 [0–4] versus 1 [0–3]), without difference after adjustment for age. Lobar atrophy and focal hypometabolism/hypoperfusion were not different between groups. The median CSF Aβ1-42 and phosphorylated tau (P-tau) concentrations were in the normal range and comparable between groups. Axonal neurodegeneration biomarkers were within the normal range (CSF T-tau; plasma T-tau in late-onset bvFTD) or higher (plasma neurofilament light chain (NFL); plasma T-tau in presenile bvFTD) than the normal values, but globally not different between bvFTD groups. Plasma glial fibrillary acid protein (GFAP) was strongly increased in both bvFTD groups compared with the values in controls of the same age. Conclusion:The CSF and plasma biomarker profiles did not suggest a more aggressive neurodegeneration in the presenile group (comparable T-tau, NFL, and GFAP levels) or the co-existence of Alzheimer’s disease in the late-onset group (comparable and within normal range CSF Aβ1-42 and P-tau). The severity of the neurodegenerative process seems comparable in presenile and late-onset bvFTD.

Keywords: Biomarkers, cerebrospinal fluid, frontotemporal dementia, glial fibrillary acid protein, late-onset, neurofilament light chain

DOI: 10.3233/JAD-190378

Journal: Journal of Alzheimer's Disease, vol. 74, no. 3, pp. 903-911, 2020