Diagnostic and therapeutic potential of exosomes in Alzheimer’s disease

Abstract

Exosomes are small extracellular vesicles released by almost all cell types in physiological and pathological conditions. The exosomal potential to unravel disease mechanisms, or to be used as a source of biomarkers, is being explored, in particularly in the field of neurodegenerative diseases. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the world and exosomes appear to have a relevant role in disease pathogenesis. This review summarizes the current knowledge on exosome contributions to AD as well as their use as disease biomarker resources or therapeutic targets. The most recent findings with respect to both protein and miRNA biomarker candidates for AD, herein described, highlight the state of the art in this field and encourage the use of exosomes derived from biofluids in clinical practice in the near future.

Uptake and Fate of Extracellular Membrane Vesicles: Nucleoplasmic Reticulum-Associated Late Endosomes as a New Gate to Intercellular Communication

“…Thus, EVs represent a heterologous population in a given biofluid. Specific isolation of their subpopulations is now an emerging challenge in the field, particularly when the purpose is to use EVs (or their cargo) as potential clinical biofluid markers [ 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. We could not exclude that distinct EVs interact with each other, resulting in their co-purification [ 30 ].…”

Vesicular Transport of Encapsulated microRNA between Glial and Neuronal Cells

“…Exosomes (EXs): (i) were first characterized about ~40 years ago as a heterogeneous group of cell cytoplasm-derived intracellular micro-particles (MPs) of endosomal origin (also known as ectosomes, shedding vesicles, microvesicles or EMVs); (ii) are variable in their content and morphology, ranging in size from about ~30 to ~100 nm in diameter; (iii) are released by a variety of central nervous system (CNS) cells whose function was originally described as a cytological basis for intercellular signaling and communication (Trams et al 1981 [ 12 ]; Columbo et al, 2014 [ 13 ]; Jiang et al, 2019 [ 14 ]; Mathews and Levy 2019 [ 15 ]; Arbo et al, 2020 [ 6 ]; Martins et al, 2020 [ 16 ]). EXs originated as intracellular endosomes containing intraluminal vesicles (ILV) that fuse with the plasma membrane and empty their plasma membrane-encapsulated cargo.…”

Extracellular Vesicles Loaded miRNAs as Potential Modulators Shared Between Glioblastoma, and Parkinson’s and Alzheimer’s Diseases

“…Recently, one revision of exosomes modulating AD has classified EVs-miRNAs according to the biological fluids collected for the study ( Martins et al, 2020 ). They observed that miRNAs in serum-derived EVs were often upregulated, whereas in plasma, were mostly downregulated.…”

“…In plasma-derived EVs, miRNA-21, miRNA-23a, miRNA-132, miRNA-193b, and miRNA-338 are downregulated ( Martins et al, 2020 ). Notably, miRNA-23a shows an opposite accumulation between serum and plasma.…”

“…Also, tumor cells can communicate with and regulate microenvironment functioning through several mechanisms, including EVs and signaling molecules. In NDDs, cells also interact to modulate the microenvironment; for example, microglia is able to secrete pro-inflammatory factors via EVs, while astrocytes secrete EVs that drive apoptosis, generating changes in the microenvironment (for details refer to Martins et al, 2020 ). Therefore, modification of the microenvironment appears to be an important shared factor for the progression of both cancer and NDDs.…”