Neuronal and Astrocytic Extracellular Vesicle Biomarkers in Blood Reflect Brain Pathology in Mouse Models of Alzheimer's Disease

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 fr...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2021-04, Vol.10 (5), p.993
Main Authors: Delgado-Peraza, Francheska, Nogueras-Ortiz, Carlos J, Volpert, Olga, Liu, Dong, Goetzl, Edward J, Mattson, Mark P, Greig, Nigel H, Eitan, Erez, Kapogiannis, Dimitrios
Format: Article
Language:English
Subjects:
Alzheimer's disease
Alzheimer’s
Animal models
Antibodies
Biomarkers
Biopsy
Brain
Cerebral cortex
Complement component C1q
exosomes
extracellular vesicles
Hippocampus
Membranes
Mutation
Neurodegenerative diseases
Neurological diseases
Pathology
Phosphatase
Plasma
Precision medicine
Proteins
Tau
Tau protein
transgenic
β-Amyloid
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Summary: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 ( = 0.03) and p181-Tau ( = 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, = 0.009; p181-Tau: cortex, r = 0.7, < 0.0001; hippocampus, r = 0.6, < 0.0001). NEVs from 5xFAD compared to other mice had higher Aβ42 ( < 0.005). NEV Aβ42 had moderately strong correlations with Aβ42 in cortex (r = 0.6, = 0.001) and hippocampus (r = 0.7, < 0.0001). AEV C1q was elevated in 3xTg-AD compared to WT mice ( = 0.005); AEV C1q had moderate-strong correlations with C1q in cortex (r = 0.9, < 0.0001) and hippocampus (r = 0.7, < 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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10050993