This conference proceedings review synthesizes findings from the Tau Global Conference 2025 (London, April 2025), covering advances in tau biology (lysosomal degradation, propagation, experimental models), biomarker development (fluid, PET, extracellular vesicles), therapeutic strategies (anti-tau antibodies, master protocol trials), and global research equity initiatives across primary and secondary tauopathies including AD, PSP, CBD, and FTLD.
Key advances include: (1) lysosomal cathepsins cleave tau at sites where MAPT mutations map, and tau phosphorylation at p-tau181/217 sites resists cleavage—potentially explaining their biomarker utility; (2) etalanetug (E2814), an anti-MTBR IgG1 antibody, produced dose-dependent CSF p-tau217 reductions of ~35–50% and MTBR-tau243 reductions of ~50–75% in dominantly inherited AD (Phase 1b); (3) [18F]-PI-2620 tau-PET can detect and longitudinally track 4R tau pathology in PSP and CBS; (4) plasma EV tau isoforms distinguished PSP and FTD from controls and other neurodegenerative diseases; (5) semorinemab showed a significant cognitive signal in mild-to-moderate AD (Lauriet) despite no measurable effect on tau pathology biomarkers.
- Conference proceedings format: findings reflect expert summaries rather than primary data, limiting direct appraisal of methodology and effect sizes. - Most genetic and biomarker data derive from European or North American cohorts, limiting generalizability to diverse populations. - Several cited studies (e.g., etalanetug Phase 1b, tau propagation models) are preliminary or preprint, pending peer-reviewed validation.
Plasma p-tau217 can now stratify CBS patients by underlying tau type (4R vs. AD tau), which may guide enrolment into tau-targeted trials—clinicians should consider it when evaluating atypical parkinsonian syndromes. Emerging master protocol designs (Alzheimer's Tau Platform, PSP Trial Platform) offer new routes for patients with AD or PSP to access experimental tau therapies starting in 2026.
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