Add like
Add dislike
Add to saved papers

Nanoscale reorganization of synaptic proteins in Alzheimer's disease.

AIMS: Synaptic strength depends strongly on the subsynaptic organization of presynaptic transmitter release and postsynaptic receptor densities, and their alterations are expected to underlie pathologies. While synaptic dysfunctions are common pathogenic traits of Alzheimer's disease (AD), it remains unknown whether synaptic protein nano-organization is altered in AD. Here, we systematically characterized the alterations in the subsynaptic organization in cellular and mouse models of AD.

METHODS: We used immunostaining and super-resolution stochastic optical reconstruction microscopy (STORM) imaging to quantitatively examine the synaptic protein nano-organization in both Aβ1-42-treated neuronal cultures and cortical sections from a mouse model of AD, APP23 mice.

RESULTS: We found that Aβ1-42-treatment of cultured hippocampal neurons decreased the synaptic retention of postsynaptic scaffolds and receptors and disrupted their nanoscale alignment to presynaptic transmitter release sites. In cortical sections, we found that while GluA1 receptors in wild-type mice were organized in subsynaptic nanoclusters with high local densities, receptors in APP23 mice distributed more homogeneously within synapses. This reorganization, together with the reduced overall receptor density, led to reduced glutamatergic synaptic transmission. Meanwhile, the transsynaptic alignment between presynaptic release-guiding RIM1/2 and postsynaptic scaffolding protein PSD-95 was reduced in APP23 mice. Importantly, these reorganizations were progressive with age and were more pronounced in synapses in close vicinity of Aβ plaques with dense cores.

CONCLUSIONS: Our study revealed a spatiotemporal-specific reorganization of synaptic nanostructures in AD and identifies dense-core amyloid plaques as the major local inductor in APP23 mice.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app