Engineering extracellular vesicles for Alzheimer's disease: An emerging cell-free approach for earlier diagnosis and treatment

Abstract

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder affecting over five million people globally and has no established cure. Current AD-related treatments only alleviate cognitive and behavioral symptoms and do not address disease onset or progression, underlining the unmet need to create an effective, innovative AD therapeutic. Extracellular vesicles (EVs) have emerged as a new class of nanotherapeutics. These secreted, lipid-bound cellular signaling carriers show promise for potential clinical applications for neurodegenerative diseases like AD. Additionally, analyzing contents and characteristics of patient-derived EVs may address the unmet need for earlier AD diagnostic techniques, informing physicians of altered genetic expression or cellular communications specific to healthy and diseased physiological states. There are numerous recent advances in regenerative medicine using EVs and include bioengineering perspectives to modify EVs, target glial cells in neurodegenerative diseases like AD, and potentially use EVs to diagnose and treat AD earlier. This article is categorized under: Neurological Diseases > Biomedical Engineering Neurological Diseases > Molecular and Cellular Physiology Neurological Diseases > Stem Cells and Development.

Keywords: Alzheimer's diagnosis; Alzheimer's disease; Alzheimer's treatment; extracellular vesicles; glial cells.

Figure 1.

Extracellular vesicles as diagnostics and therapeutics. Diagram representing (A) the utility of EV samples from Alzheimer’s patients in diagnosing, and (B) how EVs can be generated in labs and engineered as a bench-to-bedside clinical therapeutic for Alzheimer’s patients.

Figure 2.

Overview of extracellular vesicle engineering. EVs can be modified once they are collected and purified from parent cells and can include A) new surface markers, B) have new molecules physically conjugated to their existing surface markers, or C) contain new cargo macromolecules.

Figure 3.

Cellular modification to generate engineered extracellular vesicles. Parent cells that will secrete the desired EVs can be modified genetically or induced through electroporation or diffusion to take up specific cargo to incorporate into EVs.