Non-fibrillar amyloid-β (Aβ) plaques are considered to be a critical component of Alzheimer’s disease. Characterization of these species comes mainly from studies in cellular or animal models, but there is little data in intact human samples due to the lack of adequate optical microscopic resolution to study these small structures.
Marta Querol-Vilaseca in collaboration with other members of the Sant Pau Memory Unit and investigators from Institut de Ciències Fotòniques (ICFO), the University of Edinburgh and the Neurological Tissue Bank in Barcelona, has just published her research entitled “Nanoscale structure of amyloid-β plaques in Alzheimer’s disease” in the journal Scientific Reports.
What was done in this study?
In this study, we applied two super-resolution techniques, Array Tomography and Stimulated Emission Depletion microscopy (STED), to characterize the non-fibrillar Aβ structures present in amyloid plaques in postmortem human brain tissue of cases with familial and sporadic Alzheimer.
Our study shows that the combination of these two techniques, Array Tomography and STED, can be successfully applied to investigate non-fibrillar Aβ structures in human brain. We reconstructed a whole human amyloid plaque and established that plaques are formed by a dense core of large Aβ species and a peripheral halo of smaller Aβ structures. We also provide evidence of higher levels of non-fibrillar Aβ species in familial Alzheimer disease compared to sporadic cases.
Relevance of the study
This work indicates the importance of super-resolution techniques for the neuropathology field allowing the characterization of aggregates or structures at a nanometric scale as potential therapeutic targets.