3D Mapping Reveals Network-specific Amyloid Progression and Subcortical Susceptibility.

Canter, R. G.; Choi, H.; Wang, J.; Watson, L. A.; Yao, C. G.; Abdurrob, F.; Bousleiman, S. M.; Delalle, I.; Chung, K.; Tsai, L.-H.

doi:10.1101/116244

bioRxiv · 10.1101/116244

3D Mapping Reveals Network-specific Amyloid Progression and Subcortical Susceptibility.

Canter, R. G.·Choi, H.·Wang, J.·Watson, L. A.·Yao, C. G.·Abdurrob, F.·Bousleiman, S. M.·Delalle, I.·Chung, K.·Tsai, L.-H.

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Abstract

Alzheimers disease is a progressive, neurodegenerative condition for which there is no cure. Prominent hypotheses posit that accumulation of beta-amyloid (A{beta}) peptides drives the neurodegeneration that underlies memory loss, however the spatial origins of the lesions remain elusive. Using SWITCH, we created a spatiotemporal map of A{beta} deposition in a mouse model of amyloidosis. We report that structures connected by the fornix show primary susceptibility to A{beta} accumulation and demonstrate that aggregates develop in increasingly complex networks with age. Notably, the densest early A{beta} aggregates occur in the mammillary body coincident with electrophysiological alterations. In later stages, the fornix itself also develops overt A{beta} burden. Finally, we confirm A{beta} in the mammillary body of postmortem patient specimens. Together, our data suggest that subcortical memory structures are particularly vulnerable to A{beta} deposition and that functional alterations within and physical propagation from these regions may underlie the affliction of increasingly complex networks.\n\nAuthor ContributionsRGC, KC, L-HT, ID conceived of the work and planned the experiments.\n\nRGC, HC, JW, LAW, CGY, FA, SMB performed experiments and analyzed data.\n\nHC built the custom microscope.\n\nRGC, L-HT, KC, ID wrote the manuscript.

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Canter, R. G., Choi, H., Wang, J., Watson, L. A., Yao, C. G., Abdurrob, F., Bousleiman, S. M., Delalle, I., Chung, K., Tsai, L.-H.. 2017-03-13. 3D Mapping Reveals Network-specific Amyloid Progression and Subcortical Susceptibility.. https://doi.org/10.1101/116244

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