Advances in Nanotechnology - Engineered Exosomes for Early Biomarker Detection and Therapy in Alzheimer's Disease - Figure 1

Abstract

Exosomes are nanosized extracellular vesicles (30–150 nm) generated through an endosomal lysosomal pathway. They are released by all cell types, including neurons, astrocytes, oligodendrocytes, and microglia (Figure 1) (Zhao et al., 2023). The exosome’s cargo reflects the parent cell’s physiological or pathological condition and carries specific amyloid precursor protein(APP), tau protein, lipids, messenger RNAs and microRNAs (Park et al., 2024; Chen et al., 2019; Kapogiannis et al., 2014). This allows the exosomes to function as active mediators of intercellular communication within the brain microenvironment. Evidence shows that exosomes transport pathological amyloid-β (A-β) peptides as well as hyperphosphorylated tau proteins across the BBB, thereby contributing to amyloid plaque formation and neurofibrillary tangle propagation (Lakshmi et al., 2020). Tau-containing exosomes are released from affected neurons and spread along neuroanatomically connected brain regions, with various cell types such as microglia contributing to tauopathy progression (Pérez et al., 2019). The activated microglia-derived exosome can also amplify inflammatory cascades, while dysfunctional neuronal cell-derived exosomes can act as damage signals to unveil further glial attack (Lukiw & Pogue, 2020; Li et al., 2022). Collectively, these episodes exacerbate disease progression in AD (Lakshmi et al., 2020; Park et al., 2024; Kapogiannis et al., 2014; Pérez et al., 2019; Lukiw & Pogue, 2020; Li et al., 2022).