STochastic Optical Reconstruction Microscopy (STORM) reveals the nanoscale organization of pathological aggregates in human brain

Abstract Background Histological analysis of brain tissue samples provide valuable information about the pathological processes leading to common neurodegenerative disorders such as Alzheimer’s or Parkinson’s diseases. In particular, high resolution and specific analysis of intra-neuronal lesions is crucial to understand the pathogenesis and progression of these diseases. In this context, the development of novel imaging approaches is a current challenge in neuroscience. Methods To this end, we used a recent super-resolutive imaging technique called STochastic Optical Reconstruction Microscopy (STORM) to analyze human brain sections. We combined STORM cell imaging protocols with neuropathological techniques and imaged cryopreserved brain samples from control subjects and patients with neurodegenerative diseases. Results This approach allowed us to perform 2D-, 3D- and two-color-STORM in central nervous system tissue sections, and to characterize with a nanometer-scale precision the architecture of physiological and pathological structures in neocortex, white matter and brainstem samples. STORM proved to be particularly effective to visualize the organization of dense protein inclusions, and allowed us to image with unprecedented details Aβ, Tau, α-synuclein and TDP-43 pathological aggregates within the central nervous system of patients with neurodegenerative disorders. Conclusions STORM imaging of human brain samples opens further gates to a more comprehensive understanding of the underlying mechanisms responsible for common neurological diseases. The convenience of this technique should open a straightforward extension of its application for super-resolution imaging of the human brain, with promising avenues to current challenges in neuroscience.