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3D mapping reveals network-specific amyloid progression and subcortical susceptibility in mice
Name
s42003-019-0599-8.pdf
Description
Published version
Size
2.39 MB
Format
Adobe PDF
Checksum (MD5)
736fd4895b879609069d8d105069c5e9
Author(s)
Gail Canter, Rebecca
Huang, Wen-Chin
Choi, Heejin
Wang, Jun
Ashley Watson, Lauren
Yao, Christine G
Abdurrob, Fatema
Bousleiman, Stephanie M
Young, Jennie Z
Bennett, David A
Date Issued
2019
Journal
Communications Biology
Publisher
Springer Science and Business Media LLC
Version
Final published version
Abstract
© 2019, The Author(s). Alzheimer’s disease (AD) is a progressive, neurodegenerative dementia with no cure. Prominent hypotheses suggest accumulation of beta-amyloid (Aβ) contributes to neurodegeneration and memory loss, however identifying brain regions with early susceptibility to Aβ remains elusive. Using SWITCH to immunolabel intact brain, we created a spatiotemporal map of Aβ deposition in the 5XFAD mouse. We report that subcortical memory structures show primary susceptibility to Aβ and that aggregates develop in increasingly complex networks with age. The densest early Aβ occurs in the mammillary body, septum, and subiculum- core regions of the Papez memory circuit. Previously, early mammillary body dysfunction in AD had not been established. We also show that Aβ in the mammillary body correlates with neuronal hyper-excitability and that modulation using a pharmacogenetic approach reduces Aβ deposition. Our data demonstrate large-tissue volume processing techniques can enhance biological discovery and suggest that subcortical susceptibility may underlie early brain alterations in AD.
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
10.1038/S42003-019-0599-8
