Blood-derived APLP1+ extracellular vesicles are potential biomarkers for the early diagnosis of brain diseases | Science Advances

The early detection of neurodegenerative diseases necessitates the identification of specific brain-derived biomolecules in peripheral blood. In this context, our investigation delineates the role of amyloid precursor-like protein 1 (APLP1)—a protein predominantly localized in oligodendrocytes and neurons—as a previously unidentified biomarker in extracellular vesicles (EVs). Through rigorous analysis, APLP1 ⁺ EVs from human sera were unequivocally determined to be of cerebral origin. This assertion was corroborated by distinctive small RNA expression patterns of APLP1 ⁺ EVs. The miRNAs’ putative targets within these EVs manifested pronounced expression in the brain, fortifying their neurospecific provenance. We subjected our findings to stringent validation using Thy-1 GFP M line mice, transgenic models wherein GFP expression is confined to hippocampal neurons. An amalgamation of these results with an exhaustive data analysis accentuates the potential of APLP1 ⁺ EVs as cerebrally originated biomarkers. Synthesizing our findings, APLP1 ⁺ EVs are postulated not merely as diagnostic markers but as seminal entities shaping the future trajectory of neurodegenerative disease diagnostics.