Neuronal and Astrocytic Extracellular Vesicle Biomarkers in Blood Reflect Brain Pathology in Mouse Models of Alzheimer’s Disease
Francheska Delgado-Peraza,
Carlos J. Nogueras-Ortiz,
Olga Volpert,
Dong Liu,
Edward J. Goetzl,
Mark P. Mattson,
Nigel H. Greig,
Erez Eitan,
Dimitrios Kapogiannis
Affiliations
Francheska Delgado-Peraza
Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 212241, USA
Carlos J. Nogueras-Ortiz
Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 212241, USA
Olga Volpert
NeuroDex Inc., Natick, MA 01760, USA
Dong Liu
Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Edward J. Goetzl
Department of Medicine, University of California, San Francisco, CA 94143, USA
Mark P. Mattson
Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Nigel H. Greig
Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
Erez Eitan
NeuroDex Inc., Natick, MA 01760, USA
Dimitrios Kapogiannis
Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 212241, USA
Circulating neuronal extracellular vesicles (NEVs) of Alzheimer’s disease (AD) patients show high Tau and β-amyloid (Aβ) levels, whereas their astrocytic EVs (AEVs) contain high complement levels. To validate EV proteins as AD biomarkers, we immunocaptured NEVs and AEVs from plasma collected from fifteen wild type (WT), four 2xTg-AD, nine 5xFAD, and fifteen 3xTg-AD mice and assessed biomarker relationships with brain tissue levels. NEVs from 3xTg-AD mice had higher total Tau (p = 0.03) and p181-Tau (p = 0.0004) compared to WT mice. There were moderately strong correlations between biomarkers in NEVs and cerebral cortex and hippocampus (total Tau: cortex, r = 0.4, p = 0.009; p181-Tau: cortex, r = 0.7, p p p p = 0.001) and hippocampus (r = 0.7, p p = 0.005); AEV C1q had moderate-strong correlations with C1q in cortex (r = 0.9, p p < 0.0001). Biomarkers in circulating NEVs and AEVs reflect their brain levels across multiple AD mouse models supporting their potential use as a “liquid biopsy” for neurological disorders.
