This article, "Synaptic oligomeric tau in Alzheimer's disease – a potential culprit in the spread of tau pathology through the brain," published in *Neuron* by Colom-Cadena et al. (2023), examines the role of synaptic oligomeric tau in Alzheimer's disease (AD). Using sub-diffraction-limit microscopy, the researchers identified oligomeric tau at synapses in both human postmortem brain tissue and a mouse model, highlighting its potential contribution to the spread of tau pathology across brain regions. The study demonstrated that oligomeric tau was more abundant in synapses compared to phosphorylated or misfolded tau, and that it was present even in areas without neurofibrillary tangles (NFTs), suggesting that synaptic tau accumulation is an early event in AD progression.

The researchers also found that synaptic oligomeric tau accumulates in both presynaptic and postsynaptic terminals, supporting the hypothesis that tau pathology spreads trans-synaptically in Alzheimer's disease. The presence of tau at synaptic terminals even in regions with minimal NFT burden strengthens the idea that synaptic tau plays a pivotal role in AD's early pathological processes. Further, the study revealed that synaptic tau, especially oligomeric species, correlates with local synapse loss and cognitive decline, indicating its synaptotoxic potential. Advanced imaging techniques, such as immunogold electron microscopy and DNA-PAINT, confirmed tau's localization at synaptic sites.

Overall, this research provides compelling evidence that synaptic oligomeric tau is a key player in the propagation of tau pathology and synapse loss in Alzheimer's disease. The findings suggest that targeting oligomeric tau at synapses could be a promising therapeutic approach to slowing or halting AD progression. The study bridges significant gaps in understanding tau's role at the synaptic level, opening new avenues for therapeutic strategies aimed at preventing the spread of tau and preserving synaptic function in Alzheimer's patients.