3D mapping reveals network-specific amyloid progression and subcortical susceptibility in mice

Rebecca Gail Canter, Wen Chin Huang, Heejin Choi, Jun Wang, Lauren Ashley Watson, Christine G. Yao, Fatema Abdurrob, Stephanie M. Bousleiman, Jennie Z. Young, David A. Bennett, Ivana Delalle, Kwanghun Chung, Li Huei Tsai

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2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number360
JournalCommunications Biology
Volume2
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

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    Gail Canter, R., Huang, W. C., Choi, H., Wang, J., Ashley Watson, L., Yao, C. G., Abdurrob, F., Bousleiman, S. M., Young, J. Z., Bennett, D. A., Delalle, I., Chung, K., & Tsai, L. H. (2019). 3D mapping reveals network-specific amyloid progression and subcortical susceptibility in mice. Communications Biology, 2(1), [360]. https://doi.org/10.1038/s42003-019-0599-8