AbstractBackgroundExtracellular vesicles (EVs) are nano‐sized membranous particles that are released by almost all cells in the human body. EVs carry different cargo (e.g. protein, lipid, nucleic acids) that differs based on the EVs biogenesis and state of the cell during the release. Therefore, EVs are excellent for identifying disease patterns and biomarkers. The need to understand the pathogenetic patterns and biomarkers in neurodegenerative diseases is crucial for early diagnosis as well as potential therapeutic intervention.Studies show that small RNA, especially miRNA participate in pathologic processes connected to neurodegeneration, therefore we have specifically looked into microglia and neuron derived EVs small RNA content of patients with Alzheimer’s disease (AD) and control patients. The aim of the study was to find AD patterns coded in small RNA.MethodEVs were isolated specifically from microglia and neurons by immunomagnetic precipitation from blood plasma and cerebrospinal fluid (CSF) collected from patients with AD and healthy aged‐matched controls. Western blots were used to characterize EVs composition and assess purity. Small RNA isolation was performed on the isolate EVs and then sequenced using commercial kits. Quantitative PCR (qPCR) was performed for validation.ResultWe found that neuron‐ and microglia‐derived EVs are present in blood plasma as well as CSF and they carry a big variety of small RNA biotypes. Looking specifically into miRNA, distinct groups of miRNA were expressed only in AD patients and only in healthy controls. Also, differences between genders was observed.ConclusionWe showed distinct miRNA patterns in neurodegeneration, specifically in AD. The results of our study suggest that miRNA could be used to elucidate the pathological processes involved in AD development and help to diagnose neurodegenerative changes earlier.