Internalization of extracellular Tau oligomers in Alzheimer's disease

A key factor in the progression of Alzheimer's disease (AD) is internalization of extracellular Tau oligomers (ecTauOs) by neuroglial cells. Aberrant hyperphosphorylation of Tau results in their dissociation from microtubules and formation of toxic intracellular Tau oligomers (icTauOs). These are subsequently released to the extracellular space following neuronal dysfunction and death. Although receptor mediated internalization of these ecTauOs by other neurons, microglia and astrocytes can facilitate elimination, incomplete degradation thereof promotes inflammation, exacerbates pathologic spread and accelerates neurodegeneration. Targeting Tau oligomer degradation pathways, blocking internalization receptors, and mitigating neuroinflammation are proposed as therapeutic strategies to control Tau propagation and toxicity. This review highlights the urgent need for innovative approaches to prevent the spread of Tau pathology, emphasizing its implications for AD and related neurodegenerative diseases.