Abstract
Neuropathol Appl Neurobiol. 2025 Apr;51(2):e70010. doi: 10.1111/nan.70010.
ABSTRACT
AIMS: In Alzheimer's disease (AD), the pathological accumulation of tau in synapses contributes to synapse dysfunction and loss. However, the small and complex structure of synapses limits the investigation when using conventional techniques. In this work, we describe the combination of array tomography (AT) with two-colour direct stochastic optical reconstruction microscopy (dSTORM) to enhance lateral resolution for resolving synaptic terminals in human postmortem brain.
METHODS: We applied this combination to study synapses in brain samples (from biopsy and postmortem) from healthy subjects and pathological synaptic tau (aggregates and oligomers) in samples from AD patients.
RESULTS: AT combined with dSTORM allowed the characterisation of the orientation and shape of the synaptic terminals and the synaptic cleft. In addition, this combination confirmed the presence of oligomeric tau in synaptic terminals in AD.
CONCLUSIONS: Overall, we found that the combination of AT and two-colour dSTORM provides optimal resolution to detect pathological synaptic tau and its spatial relationship with presynaptic and postsynaptic terminals.
PMID:40025904 | DOI:10.1111/nan.70010
UK DRI Authors
