# Extracellular Vesicles in Tauopathies: Mechanisms and Applications **Authors:** Varun Nannuri, Ebaa Ababneh, Serena El Rayes, Jonhoi Smith, Kiminobu Sugaya, Jihe Zhao PMC · DOI: 10.3390/ijms27041998 · 2026-02-19 ## TL;DR This review discusses how extracellular vesicles contribute to tau-related diseases and their potential for diagnosis and treatment. ## Contribution The paper highlights the novel roles of extracellular vesicles in carrying and transmitting misfolded tau and their potential as diagnostic and therapeutic tools. ## Key findings - Extracellular vesicles can transmit misfolded tau and modulate immune responses in tauopathies. - EVs carry disease-specific biomarkers like tau, miRNAs, and mRNAs for diagnostic use in Alzheimer’s disease. - Engineered EVs show therapeutic potential for delivering neuroprotective cargo in tauopathies. ## Abstract Extracellular vesicles (EVs) are nanoscale membrane-enclosed vesicles that mediate intercellular communication and participate in both physiological and pathological signaling processes. Recent studies underscore the critical roles of EVs in the propagation of tau pathology and the diagnostic and therapeutic aspects of tauopathies, a class of neurodegenerative diseases marked by the pathological accumulation of the protein tau, contributing to cognitive decline and neuronal loss. This review aims to explore the many roles of EVs in tauopathies, emphasizing their ability to carry and transmit misfolded tau, modulate immune responses through microglial interactions, and serve as carriers of disease-specific biomarkers. We describe current findings on extravesicular tau, miRNAs, and mRNAs as diagnostic indicators in Alzheimer’s disease and related tauopathies and evaluate the therapeutic potential of both endogenous and engineered EVs for delivering therapeutic agents or neuroprotective cargo. Challenges such as isolation standardization, cargo loading efficiency, and biodistribution are also discussed, along with potential strategies to overcome them. Overall, the evidence emphasizes EVs as key players in the pathophysiology, diagnosis, and treatment of tauopathies, offering a strong and compelling platform for precision medicine and clinical applications in the future. ## Linked entities - **Proteins:** MAPT (microtubule associated protein tau) - **Diseases:** Alzheimer’s disease (MONDO:0004975) ## Full-text entities - **Genes:** MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, RMDN2 (regulator of microtubule dynamics 2) [NCBI Gene 151393] {aka BLOCK18, FAM82A, FAM82A1, PRO34163, PYST9371, RMD-2}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, YBX1 (Y-box binding protein 1) [NCBI Gene 4904] {aka BP-8, CBF-A, CSDA2, CSDB, DBPB, EFI-A}, Mir223 (microRNA 223) [NCBI Gene 723814] {aka Mirn223, miR-223, mmu-mir-223}, P2rx7 (purinergic receptor P2X, ligand-gated ion channel, 7) [NCBI Gene 18439] {aka P2X(7), P2X7R}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Bace1 (beta-site APP cleaving enzyme 1) [NCBI Gene 23821] {aka ASP2, Bace}, Gpbar1 (G protein-coupled bile acid receptor 1) [NCBI Gene 227289] {aka BG37, GPCR, GPR131, M-BAR, TGR5}, TARDBP (TAR DNA binding protein) [NCBI Gene 23435] {aka ALS10, TDP-43}, MIR384 (microRNA 384) [NCBI Gene 494333] {aka MIRN384, hsa-mir-384}, P2RX7 (purinergic receptor P2X 7) [NCBI Gene 5027] {aka P2X7}, PSPN (persephin) [NCBI Gene 5623] {aka PSP}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], RILP (Rab interacting lysosomal protein) [NCBI Gene 83547] {aka PP10141}, Bin1 (bridging integrator 1) [NCBI Gene 30948] {aka ALP-1, Amphl, BRAMP-2, SH3P9}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, Snca (synuclein, alpha) [NCBI Gene 20617] {aka NACP, alpha-Syn, alphaSYN}, MIR373 (microRNA 373) [NCBI Gene 442918] {aka MIRN373, hsa-mir-373, miRNA373, mir-373}, NRGN (neurogranin) [NCBI Gene 4900] {aka RC3, hng}, APOB (apolipoprotein B) [NCBI Gene 338] {aka FCHL2, FLDB, LDLCQ4, apoB-100, apoB-48}, Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874], CDH5 (cadherin 5) [NCBI Gene 1003] {aka 7B4, CD144}, IRS1 (insulin receptor substrate 1) [NCBI Gene 3667] {aka HIRS-1}, Trem2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 83433] {aka TREM-2, Trem2a, Trem2b, Trem2c}, Apob (apolipoprotein B) [NCBI Gene 238055] {aka Apo B-100, apob-100, apob-48}, MIR20A (microRNA 20a) [NCBI Gene 406982] {aka C13orf25, MIR20, MIRH1, MIRHG1, MIRN20, MIRN20A}, Cd47 (CD47 antigen (Rh-related antigen, integrin-associated signal transducer)) [NCBI Gene 16423] {aka 9130415E20Rik, B430305P08Rik, IAP, Itgp}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, S100A8 (S100 calcium binding protein A8) [NCBI Gene 6279] {aka 60B8AG, CAGA, CFAG, CGLA, CP-10, L1Ag}, GAP43 (growth associated protein 43) [NCBI Gene 2596] {aka B-50, GAP-43, PP46}, Insr (insulin receptor) [NCBI Gene 16337] {aka 4932439J01Rik, CD220, D630014A15Rik, IR, IR-A, IR-B}, MIR1323 (microRNA 1323) [NCBI Gene 100302255] {aka MIRN1323, hsa-mir-1323, mir-1323}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, MIR1225 (microRNA 1225) [NCBI Gene 100188847] {aka MIRN1225}, PYCARD (PYD and CARD domain containing) [NCBI Gene 29108] {aka ASC, CARD5, TMS, TMS-1, TMS1}, P2rx1 (purinergic receptor P2X, ligand-gated ion channel, 1) [NCBI Gene 18436] {aka P2x, Pdcd3, RP-2}, SNAP25 (synaptosome associated protein 25) [NCBI Gene 6616] {aka CMS18, DEE117, RIC-4, RIC4, SEC9, SNAP}, SYT1 (synaptotagmin 1) [NCBI Gene 6857] {aka BAGOS, P65, SVP65, SYT}, RAB7B (RAB7B, member RAS oncogene family) [NCBI Gene 338382] {aka RAB7} - **Diseases:** multiple system atrophy (MESH:D019578), amyloid (MESH:C000718787), neuronal loss (MESH:D009410), amnestic (MESH:D000425), CBS (MESH:D006712), Obesity (MESH:D009765), MSA (MESH:C537381), cognitive decline (MESH:D003072), brain tumors (MESH:D001932), Kennedy disease (MESH:D055534), memory deficits (MESH:D008569), motor dysfunction (MESH:D000068079), ALS (MESH:D008113), synaptic (MESH:D012183), Pick's disease (MESH:D020774), neuronal dysfunction (MESH:D009461), Synaptic dysfunction (MESH:C536122), FTD (MESH:D057180), progressive supranuclear palsy (MESH:D013494), neurological damage (MESH:D020196), PD (MESH:D010300), NDs (MESH:D019636), CMS (MESH:D020294), injury (MESH:D014947), Inflammatory (MESH:D007249), amyotrophic lateral sclerosis (MESH:D000690), TBI (MESH:D000070642), PART (MESH:D024801), toxicity (MESH:D064420), CNS diseases (MESH:D002493), DLB (MESH:D020961), synucleinopathy (MESH:D000080874), Neuroinflammation (MESH:D000090862), ND (MESH:C537849), AD (MESH:D000544), MCI (MESH:D060825), neurotoxic (MESH:D020258), CBD (MESH:D000088282), tumor (MESH:D009369) - **Chemicals:** lysophosphatidylethanolamine (MESH:C008301), Lipid (MESH:D008055), Catalpol (MESH:C078040), CoryB (MESH:C000600670), ceramide (MESH:D002518), Fasudil (MESH:C049347), TPP (MESH:C016136), AlloEx (-), curcumin (MESH:D003474), PC (MESH:C053518), phosphatidylcholine (MESH:D010713), Tetramethylpyrazine (MESH:C017953) - **Species:** Adeno-associated virus (species) [taxon 272636], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090] - **Mutations:** P301S - **Cell lines:** n2a — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_VM32), neuro-2a — Mus musculus (Mouse), Mouse neuroblastoma, Cancer cell line (CVCL_0470) ## Figures 2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940260/full.md --- Source: https://tomesphere.com/paper/PMC12940260