Exosomes in Alzheimer’s disease: From pathogenesis to therapeutics—A comprehensive review of diagnostic and drug delivery applications
Alzheimer's disease (AD) is still a major unmet medical challenge, with limited treatment options and a critical need for early diagnostics. Exosomes, nanoscale extracellular vesicles with a lipid bilayer, are pivotal players in intercellular communication and promising tools for AD management. Their unique ability to cross the bloodbrain barrier, low immunogenicity, and ability for cargo delivery make them ideal candidates for targeted drug delivery. This review comprehensively examines the biology of exosomes-including their structure, biogenesis, release, and uptake-and evaluates advanced methods for their isolation, purification, and characterization. We highlight their dual role in AD pathogenesis, where they can propagate pathological proteins such as amyloid-β and tau, and in therapeutic applications, where engineered exosomes deliver neuroprotective agents. Furthermore, exosomal biomarkers in biofluids show significant potential for noninvasive early diagnosis. Recent advances in loading strategies and surface engineering have been discussed, alongside challenges in scalability and safety. This synthesis bridges current knowledge with future directions, emphasizing the translational potential of exosomes in AD therapeutics and diagnostics.
Authors
- Hamed Afkhami (ORCID: https://orcid.org/0000-0002-1110-6447)
- Sharafaldin Al-Musawi (ORCID: https://orcid.org/0000-0001-9414-9663)
- Seyed Hashem Mirmazloumi
- Seyedeh Saeideh Sahraei (ORCID: https://orcid.org/0000-0002-4943-5748)
- Piao Yang
- Hamed Manoochehri (ORCID: https://orcid.org/0000-0002-7117-1857)
- Mona Shahlaei (ORCID: https://orcid.org/0000-0002-1523-4876)
- Amirhossein Ahmadieh-Yazdi (ORCID: https://orcid.org/0000-0003-0726-8555)
- Sumit Mohan (ORCID: https://orcid.org/0000-0002-5305-9685)
- Hanie Mahaki (ORCID: https://orcid.org/0000-0002-1810-9966)
- Hamid Tanzadehpanah (ORCID: https://orcid.org/0000-0002-1711-5619)
- Mohammad R. Akbari (ORCID: https://orcid.org/0000-0002-8851-3614)
- Aravind Sundararaman
- Paola Dama (ORCID: https://orcid.org/0000-0001-5716-9665)
- Mohsen Sheykhhasan (ORCID: https://orcid.org/0000-0002-4610-2278)
Institutions
- Florida State University (US)
- Mashhad University of Medical Sciences (IR)
- Shahid Sadoughi University of Medical Sciences and Health Services (IR)
- Academic Center for Education, Culture and Research (IR)
- Biotechnology Research Center (IR)
- Materials and Energy Research Center (IR)
- Ministry of Higher Education and Scientific Research (IQ)
- Islamic Azad University Tonekabon (IR)
- The Ohio State University (US)
- Bushehr University of Medical Sciences (IR)
- Qom University of Medical Science and Health Services (IR)
Publication Details
- Journal
- Biomedicine & Pharmacotherapy
- Published
- 2025-09-22
- DOI
- https://doi.org/10.1016/j.biopha.2025.118548
- Citations
- 2
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 1.61