Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration

Article type: Research Article

Authors: Benussi, Alberto^a | Ashton, Nicholas J.^{b; c; d; e} | Karikari, Thomas K.^b | Gazzina, Stefano^f | Premi, Enrico^g | Benussi, Luisa^h | Ghidoni, Roberta^h | Rodriguez, Juan Lantero^b | Emeršič, Andreja^{b; i} | Binetti, Giuliano^j | Fostinelli, Silvia^h | Giunta, Marcello^a | Gasparotti, Roberto^k | Zetterberg, Henrik^{b; i; l; m} | Blennow, Kaj^{b; i} | Borroni, Barbara^{a; *}

Affiliations: [a] Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy | [b] Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [c] Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Mölndal, Sweden | [d] King’s College London, Institute of Psychiatry, Psychology & Neuroscience, Maurice Wohl Clinical Neuroscience Institute, London, UK | [e] NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK | [f] Neurophysiology Unit, ASST Spedali Civili, Brescia, Italy | [g] Stroke Unit, ASST Spedali Civili, Brescia, Italy | [h] Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [i] Department of Neurology, University Medical Centre Ljubljana, Slovenia | [j] MAC Memory Clinic and Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [k] Neuroradiology Unit, University of Brescia, Brescia, Italy | [l] UK Dementia Research Institute at UCL, London, UK | [m] Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK

Correspondence: [*] Correspondence to: Barbara Borroni, MD, Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy. Tel.: +39 0303995632; E-mail: [email protected].

Abstract: Background:It is still unknown if serum glial fibrillary acidic protein (GFAP) is a useful marker in frontotemporal lobar degeneration (FTLD). Objective:To assess the diagnostic and prognostic value of serum GFAP in a large cohort of patients with FTLD. Methods:In this retrospective study, performed on 406 participants, we measured serum GFAP concentration with an ultrasensitive Single molecule array (Simoa) method in patients with FTLD, Alzheimer’s disease (AD), and in cognitively unimpaired elderly controls. We assessed the role of GFAP as marker of disease severity by analyzing the correlation with clinical variables, neurophysiological data, and cross-sectional brain imaging. Moreover, we evaluated the role of serum GFAP as a prognostic marker of disease survival. Results:We observed significantly higher levels of serum GFAP in patients with FTLD syndromes, except progressive supranuclear palsy, compared with healthy controls, but not compared with AD patients. In FTLD, serum GFAP levels correlated with measures of cognitive dysfunction and disease severity, and were associated with indirect measures of GABAergic deficit. Serum GFAP concentration was not a significant predictor of survival. Conclusion:Serum GFAP is increased in FTLD, correlates with cognition and GABAergic deficits, and thus shows promise as a biomarker of disease severity in FTLD.

Keywords: Biomarker, frontotemporal dementia, glial fibrillary acidic protein, magnetic resonance imaging, serum, survival, transcranial magnetic stimulation

DOI: 10.3233/JAD-200608

Journal: Journal of Alzheimer's Disease, vol. 77, no. 3, pp. 1129-1141, 2020