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Enhancing Lateral Resolution Using Two-Colour Direct Stochastic Optical Reconstruction Microscopy to Unravel Synaptic
Érika Sánchez-Aced1,2, Borja Moya-Llamas1, Joaquim Aumatell Escabias1
1Memory Unit, Department of Neurology, Institut de Recerca Sant Pau (IR Sant Pau) - Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Neuropathology and Applied Neurobiology
|March 3, 2025
Summary
Array tomography (AT) combined with two-colour direct stochastic optical reconstruction microscopy (dSTORM) reveals pathological tau in Alzheimer's disease (AD) synapses. This high-resolution technique visualizes tau's impact on synaptic structure and function.
Area of Science:
- Neuroscience
- Cell Biology
- Biophysics
Background:
- Synaptic dysfunction and loss in Alzheimer's disease (AD) are linked to pathological tau accumulation.
- Investigating synapses is challenging due to their small, complex structure, limiting conventional techniques.
Purpose of the Study:
- To combine array tomography (AT) with two-colour direct stochastic optical reconstruction microscopy (dSTORM) for enhanced lateral resolution.
- To resolve synaptic terminals and investigate pathological synaptic tau in human postmortem brain tissue.
Main Methods:
- Applied AT combined with two-colour dSTORM to human brain samples (biopsy and postmortem).
- Studied synapses from healthy subjects and AD patients with pathological synaptic tau (aggregates and oligomers).
Main Results:
- AT and dSTORM enabled characterization of synaptic terminal orientation, shape, and synaptic cleft.
- Confirmed the presence of oligomeric tau within synaptic terminals in AD samples.
Conclusions:
- The combination of AT and two-colour dSTORM offers optimal resolution for detecting pathological synaptic tau.
- This technique elucidates the spatial relationship between pathological tau and synaptic terminals in AD.
