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

Abstract

Objective We aimed to establish a method to determine whether amyloid‐β (Aβ) 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 Aβ42, Aβ42/40, 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 Aβ42 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 Aβ42, Aβ42/40, 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 Aβ42/40 and miR‐384 had potential advantages in the diagnosis of SCD.

Machine learning based on Optical Coherence Tomography images as a diagnostic tool for Alzheimer's disease

“…CSF samples (5–15 ml) were centrifuged at 2000 × g for 10 min and stored at −80°C, according to a previously established protocol. The levels of Aβ 42 , phosphorylated tau (p‐tau), and total tau (t‐tau), as well as the Aβ 42 /Aβ 40 ratios in the CSF, were measured using enzyme‐linked immunosorbent assays 26 …”

“…The levels of Aβ 42 , phosphorylated tau (p‐tau), and total tau (t‐tau), as well as the Aβ 42 /Aβ 40 ratios in the CSF, were measured using enzyme‐linked immunosorbent assays. 26 …”

Exosomes in brain diseases: Pathogenesis and therapeutic targets

“…182,183 miR-29c-3p, miR-384, and nerve cell adhesion molecule in double-labeled exosomes have the potential for early diagnosis of AD. 184,185 Serum exosomal miR-185-5p was significantly downregulated in AD patients and mice as compared with the control group. Overexpression of neuronal APP (amyloid precursor protein) regulates the levels of miR-185-5p in exosomes, thereby preventing the miR-185-5p-mediated translational repression of APP transcripts.…”

“…miRNAs, such as miR‐9‐5p, miR‐598, miR‐125b, miR‐29, miR‐342‐3p, and miR‐193b, are highly stable and resistant to degradation in exosomes before the onset of AD, suggesting their promising roles as biomarkers for the early clinical diagnosis and monitoring of AD 182,183 . miR‐29c‐3p, miR‐384, and nerve cell adhesion molecule in double‐labeled exosomes have the potential for early diagnosis of AD 184,185 . Serum exosomal miR‐185‐5p was significantly downregulated in AD patients and mice as compared with the control group.…”

Extracellular vesicles, from the pathogenesis to the therapy of neurodegenerative diseases

“…To further enhance the sensitivity and specificity of EV-based diagnosis, scientists have made a great effort to identify potential AD biomarkers in NDEVs, ADEV, and MDEVs isolated from plasma or serum. They demonstrated that Aβ 42/40 (AUC = 0.973) and miR-384 (AUC = 0.909) in NDEVs co-labeled with neural cell adhesion molecule (NCAM) and ATP-binding cassette transporter A1 have potential advantages in AD diagnosis [ 178 ]. In another study, miR-29c-3p in plasma NCAM/amphiphysin 1 dual-labeled NDEVs showed a good diagnostic performance for subjective cognitive decline (AUC = 0.789) and AD (AUC = 0.927) [ 179 ].…”