Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

42
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and...
42

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Immunotherapy with B28, an antibody to Aβ oligomers, potently decreases amyloid plaques, microgliosis, and memory decline in APP knock-in mice.

Cell reports·2026
Same author

Early binding of anti-amyloid antibodies to CAA drives complement activation, inflammation and ARIA in mice.

Molecular neurodegeneration·2026
Same author

iAstrocytes model cytokine influences on complement expression and neuronal network synchronization.

bioRxiv : the preprint server for biology·2026
Same author

Ex vivo comparison of ACU193 and lecanemab reveals binding differences in mouse brain.

Alzheimer's & dementia : the journal of the Alzheimer's Association·2026
Same author

Protein-guided RNA barcoding links transcriptomes to synaptic architecture.

bioRxiv : the preprint server for biology·2026
Same author

Engulfment by brain macrophages in a short-lived vertebrate.

bioRxiv : the preprint server for biology·2026

Related Experiment Video

Updated: May 6, 2026

Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
10:52

Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques

Published on: June 1, 2016

12.1K

Complement and microglia mediate early synapse loss in Alzheimer mouse models.

Soyon Hong1, Victoria F Beja-Glasser1, Bianca M Nfonoyim1

  • 1F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.

Science (New York, N.Y.)
|April 2, 2016
PubMed
Summary

Complement proteins and microglia drive early synapse loss in Alzheimer's disease (AD). Inhibiting these pathways reduces synaptic damage and microglial activity, suggesting a novel therapeutic target for AD.

More Related Videos

Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
09:33

Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease

Published on: December 26, 2016

8.5K
A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes
06:43

A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes

Published on: February 5, 2018

12.8K

Related Experiment Videos

Last Updated: May 6, 2026

Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
10:52

Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques

Published on: June 1, 2016

12.1K
Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
09:33

Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease

Published on: December 26, 2016

8.5K
A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes
06:43

A Novel In Vitro Live-imaging Assay of Astrocyte-mediated Phagocytosis Using pH Indicator-conjugated Synaptosomes

Published on: February 5, 2018

12.8K

Area of Science:

  • Neuroscience
  • Immunology
  • Pathology

Background:

  • Synapse loss is a key feature of Alzheimer's disease (AD), correlating with cognitive decline.
  • Microglia and complement system involvement in AD is typically linked to late-stage neuroinflammation.
  • The precise mechanisms and timing of microglial and complement involvement in early AD pathogenesis remain unclear.

Purpose of the Study:

  • To investigate the role of complement and microglia in mediating early synapse loss in Alzheimer's disease models.
  • To determine if inhibiting complement or microglial pathways can prevent early synaptic damage in AD.

Main Methods:

  • Utilized mouse models of Alzheimer's disease.
  • Assessed levels of C1q and its association with synapses.
  • Measured microglial phagocytic activity and synapse loss.
  • Inhibited components of the complement cascade (C1q, C3) and microglial complement receptor CR3.
  • Evaluated the impact of soluble beta-amyloid (Aβ) oligomers on synapses and long-term potentiation.

Main Results:

  • Increased C1q levels were observed at synapses prior to plaque deposition in AD mouse models.
  • Inhibition of C1q, C3, or CR3 significantly reduced phagocytic microglia and early synapse loss.
  • C1q was essential for the detrimental effects of soluble Aβ oligomers on synapses and hippocampal function.
  • Microglia were found to engulf synaptic material in a CR3-dependent manner when exposed to soluble Aβ oligomers.

Conclusions:

  • The complement cascade, initiated by C1q, and microglia play a critical role in mediating early synapse loss in Alzheimer's disease.
  • These pathways, normally involved in synaptic pruning during development, are inappropriately activated in AD.
  • Targeting the complement-dependent pathway and microglial CR3 presents a potential therapeutic strategy for preventing early synaptic damage in AD.