Cerebrospinal fluid level of proNGF as potential diagnostic biomarker in patients with frontotemporal dementia

Francesca Malerba; Rita Florio; Ivan Arisi; Chiara Zecca; Maria Teresa Dell'Abate; Giancarlo Logroscino; Antonino Cattaneo

doi:10.3389/fnagi.2023.1298307

Cerebrospinal fluid level of proNGF as potential diagnostic biomarker in patients with frontotemporal dementia

Front Aging Neurosci. 2024 Jan 25:15:1298307. doi: 10.3389/fnagi.2023.1298307. eCollection 2023.

Authors

Francesca Malerba¹, Rita Florio¹, Ivan Arisi^{1

2}, Chiara Zecca³, Maria Teresa Dell'Abate³, Giancarlo Logroscino^{3

4}, Antonino Cattaneo^{1

5}

Affiliations

¹ Fondazione European Brain Research Institute (EBRI) Rita Levi-Montalcini, Rome, Italy.
² Institute of Translational Pharmacology - National Research Council (IFT-CNR), Rome, Italy.
³ Center for Neurodegenerative Diseases and the Aging Brain, Department of Clinical Research in Neurology of the University of Bari "Aldo Moro" at "Pia Fondazione Card G. Panico" Hospital Tricase, Lecce, Italy.
⁴ Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari "Aldo Moro", Bari, Italy.
⁵ BIO@SNS Laboratory, Scuola Normale Superiore, Pisa, Italy.

Abstract

Introduction: Frontotemporal dementia (FTD) is an extremely heterogeneous and complex neurodegenerative disease, exhibiting different phenotypes, genetic backgrounds, and pathological states. Due to these characteristics, and to the fact that clinical symptoms overlap with those of other neurodegenerative diseases or psychiatric disorders, the diagnosis based only on the clinical evaluation is very difficult. The currently used biomarkers help in the clinical diagnosis, but are insufficient and do not cover all the clinical needs.

Methods: By the means of a new immunoassay, we have measured and analyzed the proNGF levels in 43 cerebrospinal fluids (CSF) from FTD patients, and compared the results to those obtained in CSF from 84 Alzheimer's disease (AD), 15 subjective memory complaints (SMC) and 13 control subjects.

Results: A statistically significant difference between proNGF levels in FTD compared to AD, SMC and controls subjects was found. The statistical models reveal that proNGF determination increases the accuracy of FTD diagnosis, if added to the clinically validated CSF biomarkers.

Discussion: These results suggest that proNGF could be included in a panel of biomarkers to improve the FTD diagnosis.

Keywords: NGF dysmetabolism; biomarker; diagnosis; frontotemporal dementia; immunoassay; neurodegenerative disease; proNGF; tauopathy.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the European Commission (MADIA no. 732678), by Regione Lazio (Public Notice “LIFE 2020,” MODIAG Project), by Fondo Ordinario Enti (FOE D.M 865/2019) in the framework of a collaboration agreement between the Italian National Research Council and EBRI (2019-2021), and with the founding of Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione. D.G.R. n. 2117 of 21.11.2018 (CUPB84I18000540002) – C.I.R.E.M.I.C. (Research Center of Excellence for Neurodegenerative Diseases and Brain Aging) – University of Bari “Aldo Moro.”