Objective: In the present study, the ABCA1 was used as a label to capture specific exosomes, the level of ABCA1-labeled exosomal microRNA-135a (miR-135a) was evaluated for the diagnosis of Alzheimer's disease (AD), especially in patients with early stages of AD. Methods: This is a preliminary research focused on the levels of ABCA1 in WBCs, RBCs, HT-22 cells, and neuron cells. The diagnostic value of ABCA1-labeled exosomal miR-135a was examined using the CSF and serum of APP/PS1 double transgenic mice, and 152 patients with SCD, 131 patients with MCI, 198 patients with DAT, and 30 control subjects. Results: The level of ABCA1 exosomes harvested from HT-22 cells and neuron culture medium was significantly higher compared to that of RBCs and WBCs (P < 0.05). The levels of ABCA1-labeled exosomal miR-135a increased in the CSF of MCI and DAT group compared to those of control group (P < 0.05), slightly increased (P > 0.05) in the serum of SCD patient group, and significantly increased in MCI and DAT patient groups compared to those of the control group (P < 0.05). Conclusion: This study outlines a method to capture specific exosomes and detect them using immunological methods, which is more efficient for early diagnosis of AD. © 2021 The Editorial Board of Biomedical and Environmental Sciences