The independence hypothesis posits that transient Aβ exposure establishes an autonomous tau-seeding program — explaining why Aβ clearance alone may fail to halt neurodegeneration if tau has already crossed into a self-propagating state. If tau autonomy is real, late-stage anti-tau therapy must succeed independent of Aβ, and the critical therapeutic window is before tau autonomy is established. This challenge has direct implications for the failure mode analysis of recent Aβ-clearing trials. Falsifiable prediction: APP/PS1 mice treated with γ-secretase inhibitor from month 6–12 (confirmed Aβ clearance by PET-equivalent ELISA) then started on anti-tau antibody (ABBV-8E12 equivalent) at month 15 should show ≥40% reduction in AT8+ NFT burden vs untreated controls at 18 months, despite re-accumulation of Aβ. Anti-Aβ antibody alone (started at 15 months) should show <15% tau reduction.