Related Experiment Video

Updated: Jun 29, 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

11.7K

Microglia use TAM receptors to detect and engulf amyloid β plaques

Youtong Huang1,2, Kaisa E Happonen1, Patrick G Burrola1

  • 1Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.

Nature Immunology
|April 16, 2021
PubMed

Insights

The TAM receptor system (Axl and Mer) is crucial for microglia to recognize and engulf amyloid plaques in Alzheimer's disease. However, this process surprisingly promotes dense-core plaque formation.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia, the brain's immune cells, play a role in Alzheimer's disease (AD).
  • TAM receptor tyrosine kinases (Axl and Mer) are implicated in AD pathogenesis.
  • The specific function of TAM receptors in microglial response to amyloid plaques is unclear.

Purpose of the Study:

  • To experimentally investigate the role of microglial TAM receptors (Axl and Mer) in Alzheimer's disease.
  • To determine how TAM signaling influences microglial interaction with amyloid-beta (Aβ) plaques.

Main Methods:

  • Analysis of microglial Axl and Mer expression in AD and mouse models.
  • Genetic ablation of Axl and Mer in the APP/PS1 mouse model.
  • Assessment of microglial plaque detection, response, organization, and phagocytosis.
  • Quantification of dense-core plaque formation.

Main Results:

  • Axl and Mer expression in microglia correlates with amyloid plaque decoration by Gas6 and phosphatidylserine in AD.
  • Genetic deletion of Axl and Mer impairs microglial ability to interact with and phagocytose Aβ plaques.
  • TAM-deficient mice exhibit reduced dense-core plaque formation compared to controls.

Conclusions:

  • The TAM receptor system is essential for microglial recognition and phagocytosis of amyloid plaques.
  • TAM-mediated microglial phagocytosis paradoxically promotes dense-core plaque development in AD models.

More Related Videos

Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia07:18

Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia

Published on: November 9, 2018

8.6K
Detecting Amyloid-β Accumulation via Immunofluorescent Staining in a Mouse Model of Alzheimer's Disease08:25

Detecting Amyloid-β Accumulation via Immunofluorescent Staining in a Mouse Model of Alzheimer's Disease

Published on: April 19, 2021

3.6K

Related Concept Videos

Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

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 microglia. Abnormal...