Brain EV‐Bound Proteins in Blood as a Robust Biomarker for Accurate Classification of Tau Tangles in the Brain

Abstract Background Brain derived Extracellular Vesicles (EVs) was isolated from blood and their containing pthogenic proteins were quantified to develop a biomarker signature for the classification of Tau aggregation in the brain. Method Brain derived EVs and their cargo were measured directly in the plasma of patients with AD and determined to be Tau‐PET positive (visual read) (n=10) and other age matched healthy controls (n = 22) at one time‐point. AD pathogenic proteins bound to EVs were quantified by in‐house custom developed immunoassays. Result A signature of a variety brain derived EV bound total tau, P‐T231‐tau, and P‐S396‐tau was able to accurately classify Tau‐PET positive AD patients from healthy controls (AUC: 0.88 – 0.93) Conclusion Brain derived EV bound total tau, P‐T231‐tau, and P‐S396‐tau in blood show good potential as biomarkers to classify Tau aggregation in the brain