Erez Eitan, United States of America
NeuroDex Inc. Research and DevelopmentAuthor Of 1 Presentation
NEURONAL AND ASTROCYTIC EXTRACELLULAR VESICLE BIOMARKERS IN BLOOD REFLECT BRAIN PATHOLOGY IN MOUSE MODELS OF ALZHEIMER'S DISEASE
Abstract
Aims
Circulating neuronal extracellular vesicles (NEVs) of Alzheimer’s disease (AD) patients show high Tau and Amyloid-beta (Aβ) levels, whereas their astrocytic EVs (AEVs) contain high complement levels. We sought to examine the association between blood neural EV and brain tissue levels of AD pathogenic proteins in AD mouse models.
Methods
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.
Results
NEVs had higher total (tTau) and p181-Tau in 3xTg-AD compared to WT mice (tTau, P=0.001; p181-Tau, P=0.002). For all groups of mice (Fig. 1a-b), NEV levels of tTau correlated significantly with those in cerebral cortex (r=0.7, p<0.0001) and hippocampus (r=0.5, P=0.0005) and NEV levels of p181-Tau with those in cerebral cortex (r=0.6, P<0.0001) and hippocampus (r=0.7, P<0.0001). NEVs from 5xFAD compared to other mice had higher Abeta42 (P<0.005). NEV Abeta42 had strong correlations with Abeta42 in cortex (r=0.6, P=0.001) and hippocampus (r=0.7, P<0.0001; Fig. 1c). AEV C1q was elevated in 3xTg-AD compared to WT mice (P=0.005); AEV C1q had strong correlations with C1q in cortex (r=0.9, P<0.0001) and hippocampus (r=0.7, P<0.0001; Fig. 1d).
Conclusions
Biomarkers in blood NEVs and AEVs reflect their brain levels across multiple AD mouse models supporting their potential use as “liquid biopsy” for AD.