Caitlin N Suire1, Erez Eitan1, Nancy Chiles Shaffer2, Qu Tian2, Stephanie Studenski2, Mark P Mattson1, Dimitrios Kapogiannis3. 1. Laboratory of Neurosciences, National Institute on Aging on Intramural Research Program, Baltimore, MD 21224, United States. 2. Translational Gerontology Branch, National Institute on Aging on Intramural Research Program, Baltimore, MD 21224, United States. 3. Laboratory of Neurosciences, National Institute on Aging on Intramural Research Program, Baltimore, MD 21224, United States. Electronic address: kapogiannisd@mail.nih.gov.
Abstract
BACKGROUND: Brain-derived neurotrophic factor (BDNF) is produced by cleavage of proBDNF, and BDNF and proBDNF may play antagonistic roles in nervous system development, learning, memory and neuronal stress resistance. BDNF and proBDNF are present in blood, but the origin and relative contributions of soluble and extracellular vesicle (EV)-associated levels are unknown. METHODS: In this study we used validated immunoassays to measure proBDNF and BDNF levels in plasma, total plasma EVs and a subpopulation of EVs enriched for neuronal origin (expressing the neuronal marker L1CAM) in 150 Baltimore Longitudinal Study of Aging participants with and without decline in walking speed (reflecting aging-associated motor decline). RESULTS: Levels of BDNF and proBDNF were highest in L1CAM+ EVs. Participants with walking speed decline had higher levels of proBDNF in L1CAM+ EVs compared to non-decliners, but no differences in proBDNF levels in plasma and total EV. CONCLUSIONS: Our findings suggest that levels of proBDNF and BDNF in circulating L1CAM+ EVs might be used as biomarkers for conditions involving altered BDNF signaling. Published by Elsevier Inc.
BACKGROUND:Brain-derived neurotrophic factor (BDNF) is produced by cleavage of proBDNF, and BDNF and proBDNF may play antagonistic roles in nervous system development, learning, memory and neuronal stress resistance. BDNF and proBDNF are present in blood, but the origin and relative contributions of soluble and extracellular vesicle (EV)-associated levels are unknown. METHODS: In this study we used validated immunoassays to measure proBDNF and BDNF levels in plasma, total plasma EVs and a subpopulation of EVs enriched for neuronal origin (expressing the neuronal marker L1CAM) in 150 Baltimore Longitudinal Study of Aging participants with and without decline in walking speed (reflecting aging-associated motor decline). RESULTS: Levels of BDNF and proBDNF were highest in L1CAM+ EVs. Participants with walking speed decline had higher levels of proBDNF in L1CAM+ EVs compared to non-decliners, but no differences in proBDNF levels in plasma and total EV. CONCLUSIONS: Our findings suggest that levels of proBDNF and BDNF in circulating L1CAM+ EVs might be used as biomarkers for conditions involving altered BDNF signaling. Published by Elsevier Inc.
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