Imbalance in the response of pre- and post-synaptic components to amyloidopathy

Stephen, T.-L., Tamagnini, F. ORCID: https://orcid.org/0000-0002-8741-5094, Piegsa, J., Sung, K., Harvey, J., Oliver-Evans, A., Murray, T. K., Ahmed, Z., Hutton, M. L., Randall, A., O' Neill, M. J. and Jackson, J. S. (2019) Imbalance in the response of pre- and post-synaptic components to amyloidopathy. Scientific Reports, 9. 14837. ISSN 2045-2322 doi: 10.1038/s41598-019-50781-1

Abstract/Summary

Alzheimer’s disease (AD)-associated synaptic dysfunction drives the progression of pathology from its earliest stages. Aβ species, both soluble and in plaque deposits, have been causally related to the progressive, structural and functional impairments observed in AD. It is, however, still unclear how Aβ plaques develop over time and how they progressively affect local synapse density and turnover. Here we observed, in a mouse model of AD, that Aβ plaques grow faster in the earlier stages of the disease and if their initial area is > 500 µm2; this may be due to deposition occurring in the cloud part of the plaque. In addition, synaptic turnover is higher in the presence of amyloid pathology and this is paralleled by a reduction in pre- but not post-synaptic densities. Plaque proximity does not appear to have an impact on synaptic dynamics. These observations indicate an imbalance in the response of the pre- and post-synaptic terminals and that therapeutics, alongside targeting the underlying pathology, need to address changes in synapse dynamics.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/87034
Identification Number/DOI	10.1038/s41598-019-50781-1
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Publisher	Nature Publishing Group
Download/View statistics	View download statistics for this item