Serum Cathepsin S Levels Do Not Show Alterations in Different Clinical, Neuropathological, or Genetic Subtypes of Frontotemporal Dementia Patients nor in Comparison to Healthy Control Individuals

Article type: Short Communication

Authors: Heikkinen, Sami^a | Huber, Nadine^b | Katisko, Kasper^a | Kokkola, Tarja^a | Hartikainen, Päivi^c | Krüger, Johanna^{d; e; f} | Leinonen, Ville^{h; i} | Korhonen, Ville E.^a | Herukka, Sanna-Kaisa^{a; c} | Remes, Anne M.^{d; g} | Borroni, Barbara^j | Alberici, Antonella^j | Libri, Ilenia^j | Solje, Eino^{a; c} | Haapasalo, Annakaisa^{b; *}

Affiliations: [a] Institute of Clinical Medicine – Neurology, University of Eastern Finland, Kuopio, Finland | [b] A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland | [c] Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland | [d] Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland | [e] Neurocenter, Neurology, Oulu University Hospital, Oulu, Finland | [f] Medical Research Center, Oulu University Hospital, Oulu, Finland | [g] Clinical Neurosciences, University of Helsinki, Helsinki, Finland | [h] Neuro Center, Neurosurgery, Kuopio University Hospital, Kuopio, Finland | [i] Institute of Clinical Medicine –Neurosurgery, University of Eastern Finland, Kuopio, Finland | [j] Department of Neurological Sciences, University of Brescia, Brescia, Italy

Correspondence: [*] Correspondence to: Annakaisa Haapasalo, PhD, Adjunct Professor, Research Director, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70211 Kuopio, Finland. Tel.: +358 40 355 2768; E-mail: [email protected].

Abstract: Frontotemporal dementia (FTD) can manifest as diverse clinical phenotypes and is frequently caused by mutations in different genes, complicating differential diagnosis. This underlines the urgent need for valid biomarkers. Altered lysosomal and immune functions proposedly contribute to FTD pathogenesis. Cathepsins, including cathepsin S, are enzymes preferentially expressed in brain in microglia, which influence lysosomal and immune function. Here, we examined whether alterations in serum cathepsin S levels associate with specific clinical, genetic, or neuropathological FTD subgroups, but no such alterations were observed. However, further research on other lysosomal proteins may reveal new biologically relevant biomarkers in FTD.

Keywords: Biomarker, cathepsin S, C9orf72, diagnostics, frontotemporal dementia, GRN, MAPT, proteinopathy, tau, TDP-43

DOI: 10.3233/JAD-221060

Journal: Journal of Alzheimer's Disease, vol. 93, no. 2, pp. 395-401, 2023