ABCA1-Labeled Exosomes in Serum Contain Higher MicroRNA-193b Levels in Alzheimer’s Disease

Abstract

Objective. We aimed to establish a method to determine whether microRNA-193b (miR-193b) levels in ABCA1-labeled serum exosomes might serve as a marker for the diagnosis of Alzheimer’s disease. Methods. We used immunocapture methods to determine the levels of ABCA1-labeled exosomal miR-193b in cultures of white blood cells (WBCs), red blood cells (RBCs), mouse hippocampal neuron HT-22 cells, and primary mouse neuronal cells. ABCA1-labeled exosomal miR-193b levels were also evaluated in the cerebrospinal fluid (CSF) and serum of APP/PS1 double-transgenic mice, as well as control subjects ( $n=60$ ) and study participants with subjective cognitive decline (SCD, $n=89$ ), stage and mild cognitive impairment (MCI, $n=92$ ), and dementia of the Alzheimer type (DAT, $n=92$ ). Results. ABCA1 levels of exosomes harvested from the medium of HT-22 cells and neurons were significantly higher than those of RBCs and WBCs ( $P<0.05$ ). Exosomal ABCA1 from the CSF of APP/PS1 mice were transmitted to the serum of wild-type mice after injection, and high miR-193b levels were observed in both the serum and CSF after injection. The ABCA1-labeled exosomal miR-193b levels were higher in the CSF of MCI and DAT patients compared with the CSF of the control group ( $P<0.05$ ). The ABCA1-labeled exosomal miR-193b were also slightly higher ( $P>0.05$ ) in the serum of SCD patients and significantly higher in the serum of MCI and DAT patients compared with the serum of the control group ( $P<0.05$ ). Conclusion. This study provides a method to capture specific exosomes. Detection of serum exosomes labeled with ABCA1 may facilitate the early diagnosis of AD.