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Nanoscale structure of amyloid-? plaques in Alzheimer's disease.


ABSTRACT: Soluble amyloid-? (A?) is considered to be a critical component in the pathogenesis of Alzheimer's disease (AD). Evidence suggests that these non-fibrillar A? assemblies are implicated in synaptic dysfunction, neurodegeneration and cell death. However, characterization of these species comes mainly from studies in cellular or animal models, and there is little data in intact human samples due to the lack of adequate optical microscopic resolution to study these small structures. Here, to achieve super-resolution in all three dimensions, we applied Array Tomography (AT) and Stimulated Emission Depletion microscopy (STED), to characterize in postmortem human brain tissue non-fibrillar A? structures in amyloid plaques of cases with autosomal dominant and sporadic AD. Ultrathin sections scanned with super-resolution STED microscopy allowed the detection of small A? structures of the order of 100?nm. We reconstructed a whole human amyloid plaque and established that plaques are formed by a dense core of higher order A? species (~0.022?µm3) and a peripheral halo of smaller A? structures (~0.003?µm3). This work highlights the potential of AT-STED for human neuropathological studies.

SUBMITTER: Querol-Vilaseca M 

PROVIDER: S-EPMC6435662 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Soluble amyloid-β (Aβ) is considered to be a critical component in the pathogenesis of Alzheimer's disease (AD). Evidence suggests that these non-fibrillar Aβ assemblies are implicated in synaptic dysfunction, neurodegeneration and cell death. However, characterization of these species comes mainly from studies in cellular or animal models, and there is little data in intact human samples due to the lack of adequate optical microscopic resolution to study these small structures. Here, to achieve  ...[more]

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