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.

Systematic Review: microRNAs as Potential Biomarkers in Mild Cognitive Impairment Diagnosis

“…mir-200b targets the 3' untranslated region of the APP, Aβ 42 , and MGAT3 genes. Lu et al reported that serum mir-200b levels in MCI subjects were significantly higher than in AD cases; however, the mir-200b level in AD subjects was lower concerning controls (Liu et al, 2021 ). This finding suggests that miRNA families encode more complex intrinsic features than conserved motifs, inter-miRNA family relationships, or imply shared roles in specific biological pathways and regulatory mechanisms that are not yet fully understood.…”

“…Despite the advances in the biological role of miRNAs, some technical difficulties complicate the transfer of these small molecules to clinical setups as biomarkers. Some problems arise from the high conservative nature of some miRNA families (Kaczkowski et al, 2009 ), the low concentration of these molecules in biological fluids (Kayano et al, 2016 ; Yang et al, 2018 ; Liu et al, 2021 ), and that generally there is no single miRNA associated with a tissue-specific condition (Mushtaq et al, 2016 ; Swarbrick et al, 2019 ); it is more a pattern expression condition, hence it no feasible to use a single miRNAs as a biomarker (He et al, 2021 ).…”

The role of Exosomal miRNAs in cancer

“…Studies identifying neurodegeneration-associated exosomal miRNAs in the cerebrospinal fluid might analyze the usefulness of exosomes as potential biomarker carriers in neurodegenerative pathologies. MiRNA-193b overexpression could suppress amyloid precursor protein (APP) expression, showing that miRNA-193b might contribute to neurodegeneration, with a potential to act as an important AD biomarker [ 93 ]. Furthermore, miRNA-193b was detected in hippocampal specimens from AD mice.…”

Nucleic Acid Liquid Biopsies in Alzheimer’s Disease: Current State, Challenges, and Opportunities

“…Description Nucleic Acid Source miR-132 40,41 ,miR-212 40 , miR-342-5p 42 , miR-200a-3p 43 , miR-502-3p 43 , miR-142-3p 43 , miR-483-5p 43 , miR-486-5p 43 , miR-30b-5p 43 , miR-34a 44 , miR-146a 44 ncRNAs that consist of 20-22 nucleotide sequences and are important for the regulation of gene expression. Studied most in depth as a biomarker for AD miRNA Plasma miRNA-4422 45 , miR-34c 46 , miR-193b 47 , miR-125b 48,49,50,43 , miR-23a 49 , miR-26b 49 , miR-223 50 , miR22-3p 48,[51][52][53][54] Serum miR-135a 55 , miR-146a 48,53,44,56 , miRNA-9 48,46 , miR-101 46 , miR-34a 44 , miR-29a 44 , miR-29b 44 CSF miRNA-200b-5p 35 Tears tRNA-derived RNA fragments (tRFs) 57,58 composed of 73-90 nucleotides and are primarily responsible for translating the messenger RNA (mRNA) sequence into protein tRNA -5' tRNA halves 59 Serum 51A 60 , BACE1…”

“…[78][79][80] Exosomal miRNAs, due to their ability to cross the BBB unharmed, have been a major focus in this field (reviewed in 81 ). Some of the latest publications on exosomal miRNAs feature miR-193b, which was found to be significantly elevated in serum of MCI and AD patients (p < 0.05) 47 , and miR-135a, showing an increase in the CSF of MCI and AD patients compared to control (p < 0.05) 55 . A recent review highlighted the potential importance of miR-132, which was previously identified in a study of plasma exosomes of AD patients along with miR-212.…”