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

Autor: Stephen TL; Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK.; Department of Gerontology, University of Southern California, Los Angeles, California, 90089, USA., Tamagnini F; Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK.; School of Pharmacy, University of Reading, Whiteknights Campus, Hopkins Building, Reading, RG6 6LA, UK.; Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Hatherly Laboratories, University of Exeter, Exeter, EX4 4PS, UK., Piegsa J; Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK.; Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Hatherly Laboratories, University of Exeter, Exeter, EX4 4PS, UK., Sung K; Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK., Harvey J; Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK., Oliver-Evans A; Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK., Murray TK; Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK., Ahmed Z; Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK., Hutton ML; Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK., Randall A; Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Hatherly Laboratories, University of Exeter, Exeter, EX4 4PS, UK., O'Neill MJ; Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK.; AbbVie Deutschland GmbH & Co. K.G., Ludwigshafen, Germany., Jackson JS; Eli Lilly and Company, Lilly Research Centre, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK. johanna.jackson@imperial.ac.uk.; UK Dementia Research Institute at Imperial College, Department of Brain Sciences, Imperial College London, London, UK. johanna.jackson@imperial.ac.uk.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Oct 16; Vol. 9 (1), pp. 14837. Date of Electronic Publication: 2019 Oct 16.
DOI: 10.1038/s41598-019-50781-1
Abstrakt: Alzheimer's disease (AD)-associated synaptic dysfunction drives the progression of pathology from its earliest stages. Amyloid β (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 µm 2 ; this may be due to deposition occurring in the outer regions of the plaque, the plaque cloud. 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.
Databáze: MEDLINE
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