Characterizing blood‐based, microglial derived exosomes (MDEs) as biomarkers for Alzheimer’s disease

Abstract Background Recent studies suggest neuronal and astrocyte‐derived exosomes may serve as the source of biomarkers for many neurodegenerative diseases, include AD. However very few studies have characterized the biomarker potential of microglial derived exosomes. Method Plasma exosomes were extracted and precipitated from AD patients and age matched controls. Extracted exosomes were enriched against a microglial source (TMEM119) using magnetic immunocapture and fluorescence‐activated cell sorting (FACS) sorting. MDEs were characterized by size (Nanosight) and shape (TEM). Exosome marker profiling was done by western blot. MDE cargo proteins will be quantified to identify biomarkers for stages of AD using ELISA. Result Blood‐based MDEs demonstrate similar size distributions and shape to previously reported exosome preparations. Western Blot demonstrated that MDEs were positive for exosome marker Flotilin‐1; microglial markers CD68 and IBA1 and negative for astrocyte marker, GLAST. Further characterization of MDE protein cargo levels, which include AD‐related (Aβ and p‐tau) and inflammatory markers, will be analyzed and presented. Conclusion MDEs can be successfully isolated from human blood with the hope that they also demonstrate biomarker potential for AD, akin to other CNS‐derived exosomes.