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

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.

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Blog Posts
Search

Browse by Category

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


related content

Publication - Abstract

Sclerostin is a protein secreted by osteocytes that is encoded by the SOSTgene; it decreases bone formation by reducing osteoblast differentiation through inhibition of the Wnt signaling pathway.

Read More


Publication - Summary

Gaurav Sahay’s lab at Oregon Health and Science University describe a systematic study of lipid nanoparticles (LNPs) for delivering mRNA to the retina. Eleven formulations were made using NanoAssemblr technology and some were administered by subretinal injection in mice. Th...
Read More


Stay Informed

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