Tauopathies are a group of neurodegenerative diseases characterized by the accumulation of neurofibrillary tangles - hyperphosphorylated, insoluble aggregates of the microtubule-associated protein Tau. Although astrocytes, the brain’s most abundant cell type, are well known for their roles in synaptic function, tissues homeostasis, and neuroinflammation, their contribution to tauopathies remains only partially understood. Recent evidence, however, increasingly points to astrocytes playing a key role in the uptake and spread of pathological tau.
To explore this hypothesis, Khalid Eltom and colleagues at the university of Uppsala in Sweden looked into how astrocytes process and spread pathological tau aggregates. Using iPSC-derived astrocytes exposed to human brain-derived tau fibrils, they observed that while astrocytes can internalize tau fibrils, they fail to degrade them. Instead, the aggregates accumulate within the cells and are later transferred to neighbouring cells via tunneling nanotubes. This intercellular spread of tau is associated with the secretion of pro-inflammatory cytokines, triggering inflammation and subsequent neurotoxicity, impairing neuronal function.
To confirm the transfer of intracellular tau fibrils, the researchers used live-cell imaging with Amytracker 680<. The high specificity of Amytracker for amyloid-like structures allowed them to distinguish tau deposits from other cellular components and to track their movement in real time. By enabling precise fluorescence imaging, Amytracker continues to be an essential tool in unraveling protein misfolding disorders and advancing potential therapies for Alzheimer’s disease.