This review synthesizes exosome biology and translational advances across neurodegenerative diseases, emphasizing exosome-mediated propagation of misfolded proteins (including α-synuclein), disease-specific exosomal biomarkers, and engineered/ stem cell-derived exosome therapeutics for CNS delivery.

For Parkinson's research it aggregates actionable leads—α-synuclein-containing exosomes as both biomarkers and pathogenic vectors, plus strategies for exosome-based CNS delivery—while clearly outlining translational barriers (scalability, PK/PD, immunogenicity) that prioritize immediate preclinical…

Exosomes are nanoscale extracellular vesicles (EVs) that mediate intercellular communication and carry proteins, lipids, mRNAs, and non-coding RNAs reflective of their parental cells. Their biogenesis, molecular composition, and ability to traverse physiological barriers, including the blood-brain barrier, position exosomes as powerful candidates for biomarker development and therapeutic delivery in neurodegenerative diseases (NDDs). In Alzheimer's disease, Parkinson's disease, multiple sclerosis, and prion disorders, exosomes not only mirror pathological processes but actively participate in the propagation of misfolded proteins and neuroinflammatory signals through cell-type-specific vesicle subpopulations. This review synthesises current advances in exosome biology, cargo sorting, release mechanisms, and pathophysiological roles in the central nervous system, with emphasis on how neuron-, astrocyte-, and microglia-derived exosomes diverge in their cargo profiles and functional consequences across diseases. We highlight disease-specific exosomal signatures, including amyloid-β (Aβ), tau, α-synuclein, myelin proteins, prion proteins (PrP) and regulatory microRNAs. We evaluate emerging technologies such as microfluidic isolation, single-vesicle analysis, and multi-omics profiling that are accelerating biomarker discovery, and review exosome-based therapeutic strategies, including native stem cell-derived exosomes and surface-engineered vesicles loaded with neuroprotective miRNAs, small molecules, and gene-editing cargo. We address critical unmet challenges in translating these approaches to the clinic, including scalable and standardised production, incomplete pharmacokinetic /pharmacodynamic characterisation in preclinical models, immunogenicity and off-target safety concerns, and the absence of specific regulatory guidance for EV drug products. Together, these insights highlight the transformative potential of exosomes as both precision diagnostic tools and disease-modifying therapeutic platforms for NDDs.