Citations 2
Single‐extracellular vesicle (EV) analyses validate the use of L1 Cell Adhesion Molecule (L1CAM) as a reliable biomarker of neuron‐derived EVs
Nogueras‐Ortiz, Carlos , Eren, Erden , Yao, Pamela J. , Calzada, Elizabeth , Dunn, Christopher J. , Volpert, Olga V. , Delgado‐Peraza, Francheska , Lyashkov, Alexey E., Vreones, Michael , Cheng, Lesley , You, Yang , Eitan, Erez , Goetzl, Edward J. , Kapogiannis, Dimitrios , Nogueras-Ortiz, Carlos J , Volpert, Olga , Vreones, Michael , Hill, Andrew F , Ikezu, Tsuneya , Yang, You , Dunn, Christopher, Mustapić, Maja , Rubio, Francisco Javier , Hill, Andrew F. , Ikezu, Tsuneya
Journal of Extracellular Vesicles | June 13, 2024 | Volume: 13 | Issue: 6 | Pages: No page available
Abstract Isolation of neuron‐derived extracellular vesicles (NDEVs) with L1 Cell Adhesion Molecule (L1CAM)‐specific antibodies has been widely used to identify blood biomarkers of CNS disorders. However, full methodological validation requires demonstration of L1CAM in individual NDEVs and lower levels or absence of L1CAM in individual EVs from other cells. Here, we used multiple single‐EV techniques to establish the neuronal origin and determine the abundance of L1CAM‐positive EVs in human blood. L1CAM epitopes of the ectodomain are shown to be co‐expressed on single‐EVs with the neuronal proteins β‐III‐tubulin, GAP43, and VAMP2, the levels of which increase in parallel with the enrichment of L1CAM‐positive EVs. Levels of L1CAM‐positive EVs carrying the neuronal proteins VAMP2 and β‐III‐tubulin range from 30% to 63%, in contrast to 0.8%–3.9% of L1CAM‐negative EVs. Plasma fluid‐phase L1CAM does not bind to single‐EVs. Our findings support the use of L1CAM as a target for isolating plasma NDEVs and leveraging their cargo to identify biomarkers reflecting neuronal function.
Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case‐control study
Fiandaca, Massimo S. , Kapogiannis, Dimitrios , Mapstone, Mark , Boxer, Adam L. , Eitan, Erez , Petersen, Ronald C. , Federoff, Howard J. , Goetzl, Edward J. , Eitan, Erez , Schwartz, Janice B. , Abner, Erin L. , Miller, Bruce L.
Alzheimer's & Dementia | August 15, 2014 | Volume: 11 | Issue: 6 | Pages: 600
Abstract Background Proteins pathogenic in Alzheimer's disease (AD) were extracted from neurally derived blood exosomes and quantified to develop biomarkers for the staging of sporadic AD. Methods Blood exosomes obtained at one time‐point from patients with AD (n = 57) or frontotemporal dementia (FTD) (n = 16), and at two time‐points from others (n = 24) when cognitively normal and 1 to 10 years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD‐pathogenic exosomal proteins were extracted and quantified by enzyme‐linked immunosorbent assays. Results Mean exosomal levels of total tau, P‐T181‐tau, P‐S396‐tau, and amyloid β 1–42 (Aβ1–42) for AD and levels of P‐T181‐tau and Aβ1–42 for FTD were significantly higher than for case‐controls. Step‐wise discriminant modeling incorporated P‐T181‐tau, P‐S396‐tau, and Aβ1–42 in AD, but only P‐T181‐tau in FTD. Classification of 96.4% of AD patients and 87.5% of FTD patients was correct. In 24 AD patients, exosomal levels of P‐S396‐tau, P‐T181‐tau, and Aβ1–42 were significantly higher than for controls both 1 to 10 years before and when diagnosed with AD. Conclusions Levels of P‐S396‐tau, P‐T181‐tau, and Aβ1–42 in extracts of neurally derived blood exosomes predict the development of AD up to 10 years before clinical onset.