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


ABSTRACT: Alzheimer's disease (AD)-associated synaptic dysfunction drives the progression of pathology from its earliest stages. Amyloid ? (A?) 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 A? plaques develop over time and how they progressively affect local synapse density and turnover. Here we observed, in a mouse model of AD, that A? 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 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.

SUBMITTER: Stephen TL 

PROVIDER: S-EPMC6795896 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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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 s  ...[more]

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