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

Neuropathology and Applied Neurobiology
P CodronA Chevrollier

Abstract

Histological analysis of brain tissue samples provides valuable information about the pathological processes leading to common neurodegenerative disorders. In this context, the development of novel high-resolution imaging approaches is a current challenge in neuroscience. To this end, we used a recent super-resolution imaging technique called STochastic Optical Reconstruction Microscopy (STORM) to analyse human brain sections. We combined STORM cell imaging protocols with neuropathological techniques to image cryopreserved brain samples from control subjects and patients with neurodegenerative diseases. This approach allowed us to perform 2D-, 3D- and two-colour-STORM in neocortex, white matter and brainstem samples. STORM proved to be particularly effective at visualizing the organization of dense protein inclusions and we imaged with a <50 nm resolution pathological aggregates within the central nervous system of patients with Alzheimer's disease, Parkinson's disease, Lewy body dementia and fronto-temporal lobar degeneration. Aggregated Aβ branches appeared reticulated and cross-linked in the extracellular matrix, with widths from 60 to 240 nm. Intraneuronal Tau and TDP-43 inclusions were denser, with a honeycomb pattern in t...Continue Reading

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Citations

Jan 2, 2021·Frontiers in Molecular Neuroscience·Rocco PizzarelliSilvia Di Angelantonio
Mar 24, 2021·Chemical Reviews·Christian WernerChristian Geis
Aug 8, 2021·Cells·Joshua J A Poole, Leila B Mostaço-Guidolin
Nov 3, 2021·Nature Reviews. Neuroscience·Pranesh PadmanabhanJürgen Götz

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Methods Mentioned

BETA
electron microscopy
fluorescence imaging
super‐resolution microscopy
fluorescence microscopy
transmission electron microscopy
fluorescence
super resolution microscopy

Software Mentioned

PRISM
3DSTORM
STORM
Imaris
AxioVisio
Metamorph
GraphPad
Wavertracer
WaveTracer

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