Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons.

Hyperphosphorylated tau disrupts microtubule envelopes and impairs lysosome transport, contributing to neurodegeneration in tauopathies like Alzheimer's disease.

• Why it matters: Understanding how tau modifications affect neuronal transport is crucial because disrupted intracellular trafficking is a key feature of neurodegenerative diseases, yet the mechanisms remain unclear.
• What they did: Researchers used tau phospho-variants in vitro and in live neurons to examine tau’s microtubule binding, envelope formation, and effects on motor proteins and lysosome movement, analyzing over 100 neurons.
• The result: Hyperphosphorylation prevents tau envelope formation, weakens its regulation of lysosome transport, and accelerates motor protein detachment, revealing a mechanism that may underlie early neurodegenerative processes.