Neurofilament light: a possible prognostic biomarker for treatment of vascular contributions to cognitive impairment and dementia
AffiliationDepartment of Physiology, The University of Arizona
Department of Nutritional Sciences, The University of Arizona
Department of Biomedical Engineering, The University of Arizona
Sarver Molecular Cardiovascular Research Program, The University of Arizona
Department of Pharmacy, Skaggs Pharmaceutical Sciences Center, The University of Arizona
Department of Medicine, Division of Translational and Regenerative Medicine, The University of Arizona
Department of Chemistry and Biochemistry, The University of Arizona
Department of Immunobiology, The University of Arizona
Department of Epidemiology and Biostatistics, University of Arizona
Department of Neurology, The University of Arizona
Evelyn F. McKnight Brain Institute, The University of Arizona, The University of Arizona
Neurofilament light (NfL)
Vascular contributions to cognitive impairment and dementia
MetadataShow full item record
PublisherBioMed Central Ltd
CitationHoyer-Kimura, C., Konhilas, J. P., Mansour, H. M., Polt, R., Doyle, K. P., Billheimer, D., & Hay, M. (2021). Neurofilament light: A possible prognostic biomarker for treatment of vascular contributions to cognitive impairment and dementia. Journal of Neuroinflammation.
JournalJournal of Neuroinflammation
RightsCopyright © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractBackground: Decreased cerebral blood flow and systemic inflammation during heart failure (HF) increase the risk for vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer disease-related dementias (ADRD). We previously demonstrated that PNA5, a novel glycosylated angiotensin 1–7 (Ang-(1–7)) Mas receptor (MasR) agonist peptide, is an effective therapy to rescue cognitive impairment in our preclinical model of VCID. Neurofilament light (NfL) protein concentration is correlated with cognitive impairment and elevated in neurodegenerative diseases, hypoxic brain injury, and cardiac disease. The goal of the present study was to determine (1) if treatment with Ang-(1–7)/MasR agonists can rescue cognitive impairment and decrease VCID-induced increases in NfL levels as compared to HF-saline treated mice and, (2) if NfL levels correlate with measures of cognitive function and brain cytokines in our VCID model. Methods: VCID was induced in C57BL/6 male mice via myocardial infarction (MI). At 5 weeks post-MI, mice were treated with daily subcutaneous injections for 24 days, 5 weeks after MI, with PNA5 or angiotensin 1–7 (500 microg/kg/day or 50 microg/kg/day) or saline (n = 15/group). Following the 24-day treatment protocol, cognitive function was assessed using the Novel Object Recognition (NOR) test. Cardiac function was measured by echocardiography and plasma concentrations of NfL were quantified using a Quanterix Simoa assay. Brain and circulating cytokine levels were determined with a MILLIPLEX MAP Mouse High Sensitivity Multiplex Immunoassay. Treatment groups were compared via ANOVA, significance was set at p < 0.05. Results: Treatment with Ang-(1–7)/MasR agonists reversed VCID-induced cognitive impairment and significantly decreased NfL levels in our mouse model of VCID as compared to HF-saline treated mice. Further, NfL levels were significantly negatively correlated with cognitive scores and the concentrations of multiple pleiotropic cytokines in the brain. Conclusions: These data show that treatment with Ang-(1–7)/MasR agonists rescues cognitive impairment and decreases plasma NfL relative to HF-saline-treated animals in our VCID mouse model. Further, levels of NfL are significantly negatively correlated with cognitive function and with several brain cytokine concentrations. Based on these preclinical findings, we propose that circulating NfL might be a candidate for a prognostic biomarker for VCID and may also serve as a pharmacodynamic/response biomarker for therapeutic target engagement. © 2021, The Author(s).
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Except where otherwise noted, this item's license is described as Copyright © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License.