Selected publication milestones, not an exhaustive history or discovery priority claim.
2012 — Tracer and AQP4 experiments establish a restricted perivascular transport mechanism. Original PMID22896675.
2013 — Sleep-state experiments associate larger interstitial space with increased clearance in mice. Original PMID24136970.
2017 — Direct diffusion and AQP4-independent measurements challenge uniform parenchymal convection. Original PMID28826498.
2018 — Human isotope kinetics distinguishes amyloid production from fractional clearance. Original PMID29220873.
2022 — AQP4 loss worsens pathology in a mutant-tau mouse model. Original PMID35212707.
2024 — Small-dye experiments report reduced clearance during sleep and anesthesia. Original PMID38741022.
2025 — Noradrenergic oscillations link sleep microarchitecture to fluid transport. Original PMID39788123.
2026 — Endogenous neuronal protein tracing resolves compartment-specific exit routes. Original PMID42214342.
Influx, redistribution, degradation and net export need independent mass-balance measurements.
Opposite sleep results require matched injection recovery, solute size, compartment and physiological state.
AQP4 affects water homeostasis and cell function beyond the proposed route.
Human device/model estimates need held-out orthogonal clearance validation; plasma changes alone do not identify the route.
A clearance-specific human disease-trajectory intervention and directionally valid genetic instrument remain unverified.
Prospectively register a selective adult pathway manipulation in a predefined aging/neurodegeneration setting, measure endogenous-solute production and net export with independent methods, and follow neuronal/functional trajectory. Match circadian timing, natural sleep, vascular dynamics and delivery pressure; add mediator rescue or epistasis before translating the physiological target to a human clinical trial.