Cerebrospinal Fluid Neurogranin as a Biomarker of Neurodegenerative Diseases: A Cross-Sectional Study

Article type: Research Article

Authors: Lista, Simone^{a; *} | Toschi, Nicola^{b; c; d} | Baldacci, Filippo^{a; e} | Zetterberg, Henrik^{f; g} | Blennow, Kaj^{f; h} | Kilimann, Ingoⁱ | Teipel, Stefan J.ⁱ | Cavedo, Enrica^{a; j} | dos Santos, Antonio Melo^k | Epelbaum, Stéphane^k | Lamari, Foudil^l | Dubois, Bruno^k | Nisticò, Robert^m | Floris, Roberto^b | Garaci, Francesco^{b; n} | Hampel, Harald^a | for the Alzheimer Precision Medicine Initiative (APMI)

Affiliations: [a] AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris, Inserm, CNRS, Institut du Cerveau et de la Moelle Épinière (ICM), Département de Neurologie, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, Boulevard de l’hôpital, Paris, France | [b] Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy | [c] Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, USA | [d] Harvard Medical School, Boston, MA, USA | [e] Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy | [f] Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [g] Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK | [h] The Torsten Söderberg Professorship in Medicine at the Royal Swedish Academy of Sciences, Sweden | [i] Department of Psychosomatic Medicine, University of Rostock & DZNE Rostock, Rostock, Germany | [j] IRCCS “San Giovanni di Dio-Fatebenefratelli”, Brescia, Italy | [k] Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris, Inserm, CNRS, Institut du Cerveau et de la Moelle Épinière (ICM), Département de Neurologie, Institut de la Mémoire et de laMaladie d’Alzheimer (IM2A), HôpitalPitié-Salpêtrière, Boulevard de l’hôpital, Paris, France | [l] AP-HP, UF Biochimie des Maladies Neuro-métaboliques, Service de Biochimie Métabolique, Groupe Hospitalier Pitié-Salpêtrière, Paris, France | [m] Department of Biology, University ofRome “Tor Vergata” & Pharmacology of Synaptic Disease Lab, European Brain Research Institute (E.B.R.I.), Rome, Italy | [n] Casa di Cura “San Raffaele Cassino”, Cassino, Italy

Correspondence: [*] Correspondence to: Simone Lista, PhD, AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Paris 06, Inserm, CNRS, Institut du Cerveau et de la Moelle Épinière (ICM), Département de Neurologie, Institut de la Mémoire et de la Maladie d’Alzheimer (IM2A), Hôpital Pitié-Salpêtrière, 47 Boulevard de l’Hôpital, 75651 - Paris, CEDEX 13, France. Tel.: +33 1 57 27 46 74; Fax: +33 1 42 16 75 16; E-mail: [email protected].

Abstract: We investigated cerebrospinal fluid (CSF) concentrations of the postsynaptic biomarker neurogranin at baseline in cognitively healthy controls (HC) compared to individuals with mild cognitive impairment (MCI), patients with Alzheimer’s disease (AD) dementia, and patients with frontotemporal dementia (FTD). CSF neurogranin was quantified using an in-house immunoassay in a cross-sectional multicenter study of 108 participants [AD dementia (n = 35), FTD (n = 9), MCI (n = 41), cognitively HC (n = 23)]. CSF neurogranin concentrations were significantly higher in AD patients compared with both HC subjects and FTD patients, suggesting that increased CSF neurogranin concentrations may indicate AD-related pathophysiology. CSF neurogranin was independently associated with both total tau and hyperphosphorylated tau proteins, whereas a non-significant correlation with the 42-amino acid-long amyloid-β peptide was evident. CSF neurogranin, however, was not superior to core AD biomarkers in differentiating HC from the three diagnostic groups, and it did not improve their diagnostic accuracy. We conclude that further classification and longitudinal studies are required to shed more light into the potential role of neurogranin as a pathophysiological biomarker of neurodegenerative diseases.

Keywords: Alzheimer’s disease, cerebrospinal fluid, cognitive aging, frontotemporal dementia, mild cognitive impairment, neurogranin

DOI: 10.3233/JAD-170368

Journal: Journal of Alzheimer's Disease, vol. 59, no. 4, pp. 1327-1334, 2017