MicroRNA-29c-3p in dual-labeled exosome is a potential diagnostic marker of subjective cognitive decline.

OBJECTIVE: The present study aimed to determine whether peripheral blood neural cell adhesion molecule (NCAM)/amphiphysin 1 dual-labeled exosomal proteins and microRNAs (miRs) might serve as a marker for the early diagnosis of Alzheimer's disease (AD). METHODS: This observational, retrospective, multicenter study used a two-stage design conducted in Beijing and Shanghai, China. The subjects included 76 patients with subjective cognitive decline (SCD), 80 with amnestic mild cognitive impairment (aMCI), 76 with dementia of Alzheimer's type (AD), 40 with vascular dementia (VaD), and 40 controls in the discovery stage. These results were confirmed in the verification stage. The levels of Aß42, Aß42/40, T-Tau, P-T181-tau, neurofilament light chain (NfL), and miR-29c-3p in peripheral blood amphiphysin 1 single-labeled and NCAM/amphiphysin 1 dual-labeled exosomes were captured and detected by immunoassay. RESULTS: In the discovery stage, the levels of Aß42 and miR-29c-3p in peripheral blood NCAM/amphiphysin 1 dual-labeled exosome of the SCD group were significantly higher than those in control and VaD groups (all P < 0.05). The verification stage further confirmed the results of the discovery stage. Plasma NCAM/amphiphysin 1 dual-labeled exosomal miR-29c-3p showed a good diagnostic performance. The NCAM/amphiphysin 1 dual-labeled exosomal miR-29c-3p had the highest AUC for diagnosis of SCD. The levels of Aß42, Aß42/40, Tau, P-T181-tau, and miR-29c-3p in peripheral blood exosomes were correlated to those in CSF (all P < 0.05). The combination of exosomal biomarkers had slightly higher diagnostic efficiency than the individual biomarkers and that the exosomal biomarkers had the same diagnostic power as the CSF biomarkers. CONCLUSION: The plasma NCAM/amphiphysin 1 dual-labeled exosomal miR-29c-3p had potential advantages in the diagnosis of SCD.

Amyloid-ß protein and MicroRNA-384 in NCAM-Labeled exosomes from peripheral blood are potential diagnostic markers for Alzheimer's disease.

OBJECTIVE: We aimed to establish a method to determine whether amyloid-ß (Aß) protein and miR-384 in peripheral blood neural cell adhesion molecule (NCAM)/ATP-binding cassette transporter A1 (ABCA1) dual-labeled exosomes may serve as diagnostic markers for the diagnosis of Alzheimer's disease (AD). METHODS: This was a multicenter study using a two-stage design. The subjects included 45 subjective cognitive decline (SCD) patients, 50 amnesic mild cognitive impairment (aMCI) patients, 40 AD patients, and 30 controls in the discovery stage. The results were validated in the verification stage in 47 SCD patients, 45 aMCI patients, 45 AD patients, and 30 controls. NCAM single-labeled and NCAM/ABCA1 double-labeled exosomes in the peripheral blood were captured and detected by immunoassay. RESULTS: The Aß42, Aß42/40 , Tau, P-T181-tau, and miR-384 levels in NCAM single-labeled and NCAM/ABCA1 double-labeled exosomes of the aMCI and AD groups were significantly higher than those of the SCD, control, and vascular dementia (VaD) groups (all p < 0.05). The Aß42 and miR-384 levels in NCAM/ABCA1 dual-labeled exosomes of the aMCI and AD groups were higher than those of the control and VaD groups (all p < 0.05). The exosomal Aß42, Aß42/40 , Tau, P-T181-tau, and miR-384 levels in peripheral blood were correlated with those in cerebrospinal fluid (all p < 0.05). CONCLUSION: This study, for the first time, established a method that sorts specific surface marker exosomes using a two-step immune capture technology. The plasma NCAM/ABCA1 dual-labeled exosomal Aß42/40 and miR-384 had potential advantages in the diagnosis of SCD.