Changes in the Synaptic Proteome in Tauopathy and Rescue of Tau-Induced Synapse Loss by C1q Antibodies


Authors: B. Dejanovic, M.A. Huntley, A. De Mazière, W.J. Meilandt, T. Wu, K. Srinivasan and M. Sheng et al.

Journal: Neuron

DOI: 10.1016/j.neuron.2018.10.014

Publication - Abstract

November 01, 2018

Neuroscience Nucleic Acid Lipid Nanoparticles siRNA
Synapse loss and Tau pathology are hallmarks of Alzheimer’s disease (AD) and other tauopathies, but how Tau pathology causes synapse loss is unclear. We used unbiased proteomic analysis of postsynaptic densities (PSDs) in Tau-P301S transgenic mice to identify Tau-dependent alterations in synapses prior to overt neurodegeneration. Multiple proteins and pathways were altered in Tau-P301S PSDs, including depletion of a set of GTPase-regulatory proteins that leads to actin cytoskeletal defects and loss of dendritic spines. Furthermore, we found striking accumulation of complement C1q in the PSDs of Tau-P301S mice and AD patients. At synapses, C1q decorated perisynaptic membranes, accumulated in correlation with phospho-Tau, and was associated with augmented microglial engulfment of synapses and decline of synapse density. A C1q-blocking antibody inhibited microglial synapse removal in cultured neurons and in Tau-P301S mice, rescuing synapse density. Thus, inhibiting complement-mediated synapse removal by microglia could be a potential therapeutic target for Tau-associated neurodegeneration.

limit search to this category
Advanced Search

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Articles
Search

Browse by Category

  • Application
    • Diagnostic and Imaging
    • Genetic Medicine
    • Hematology
    • Metabolic Disorders
    • Neuroscience
    • Oncology
    • Skeletal Disorders
    • Targeted Drug Delivery
    • Vaccines
    • Other Applications
    • Cell therapy
  • Formulation
    • Liposomes
    • Nucleic Acid Lipid Nanoparticles
    • Polymeric Nanoparticles
    • Other Formulations
  • Payload
    • DNA
    • microRNA
    • mRNA
    • siRNA
    • Small Molecule Drugs
    • Other Payloads


related content

Publication - Abstract

Mar 18, 2021
European Journal of Pharmaceutics and Biopharmaceutics

Improved Multidetector Asymmetrical-flow fFeld-flow Fractionation Method for Particle Sizing and Concentration Measurements of Lipid-based Nanocarriers for RNA Delivery

R. Mildner, S. Hak, J. Parot, A. Hyldbakk, S.E. Borgos, D. Some, C. Johann and F. Caputo

Other Applications Nucleic Acid Lipid Nanoparticles microRNA

Use of the frit-inlet channel improves MD-AF4 analysis of LNP-RNA.

A robust method for AF4 separation of LNP-RNA has been developed and tested on two different platform.

The method meets all the ISO stan...

Read More


Publication - Summary

Sep 24, 2018
Nucleic Acid Therapeutics

MicroRNAs Enable mRNA Therapeutics to Selectively Program Cancer Cells to Self-Destruct

R. Jain, J.P. Frederick, E.Y. Huang, K.E. Burke, D.M. Mauger, E.A. Andrianova, S.J. Farlow, S. Siddiqui, J. Pimentel, K. Cheung-Ong, K.M. McKinney, C. Köhrer, M.J. Moore and T. Chakraborty

Nucleic Acid Lipid Nanoparticles mRNA Oncology
The advent of therapeutic mRNAs significantly increases the possibilities of protein-based biologics beyond those that can be synthesized by recombinant technologies (eg, monoclonal antibodies, extracellular enzymes, and cytokines). In addition to their application in the areas o...
Read More


Sign Up and Stay Informed
Sign up today to automatically receive new Precision NanoSystems application notes, conference posters, relevant science publications, and webinar invites.
Sign Up