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CCL2 affects β-amyloidosis and progressive neurocognitive dysfunction in a mouse model of Alzheimer's disease

Tomomi Kiyota1, Howard E Gendelman, Robert A Weir

  • 1Center for Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 5930, USA. tkiyota@unmc.edu

Neurobiology of Aging
|October 9, 2012
PubMed

Insights

CC-chemokine ligand 2 (CCL2) deficiency exacerbates Alzheimer's disease (AD) progression by impairing beta-amyloid (Aβ) clearance and microglial function, accelerating memory deficits in mice.

Area of Science:

  • Neuroscience
  • Immunology
  • Pathobiology

Background:

  • Neuroinflammation is a key factor in Alzheimer's disease (AD) pathogenesis.
  • Beta-amyloid (Aβ) deposition triggers microglial activation and pro-inflammatory responses.
  • Microglial plasticity allows shifts between toxic and trophic states, regulated by signaling pathways.

Purpose of the Study:

  • To investigate the role of CC-chemokine ligand 2 (CCL2) and its receptor (CC-chemokine receptor 2) signaling in AD.
  • To determine how CCL2 deficiency impacts disease progression and behavioral abnormalities in AD mouse models.

Main Methods:

  • Utilized Aβ precursor protein/presenilin-1 double-transgenic mice to model AD.
  • Assessed behavioral abnormalities and disease progression in CCL2-deficient mice compared to controls.
  • Analyzed Aβ deposition, oligomer formation, and peripheral Aβ clearance.

Main Results:

  • CCL2 deficiency led to increased cortical and hippocampal Aβ deposition and oligomer formation.
  • Impaired peripheral Aβ clearance and reduced function of scavenger, neuroprogenitor, and microglial cells were observed.
  • These deficits were linked to deficient Aβ uptake, accelerating memory dysfunction.

Conclusions:

  • CCL2 plays a significant role in innate immune responses relevant to AD pathogenesis.
  • CCL2 signaling is critical for microglial function and Aβ clearance in the context of AD.
  • Targeting CCL2 may offer a therapeutic strategy for mitigating AD progression.

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