Skip to Content
Merck
  • MyD88 is dispensable for cerebral amyloidosis and neuroinflammation in APP/PS1 transgenic mice.

MyD88 is dispensable for cerebral amyloidosis and neuroinflammation in APP/PS1 transgenic mice.

The American journal of pathology (2014-09-02)
Tara M Weitz, David Gate, Kavon Rezai-Zadeh, Terrence Town
ABSTRACT

Activated microglia are associated with amyloid plaques in transgenic mouse models of cerebral amyloidosis and in human Alzheimer disease; yet, their implication in Alzheimer disease pathogenesis remains unclear. It has been suggested that microglia play dual roles depending on the context of activation, contributing negatively to disease pathogenesis by secreting proinflammatory innate cytokines or performing a beneficial role via phagocytosis of amyloid beta (Aβ) deposits. Toll-like receptors, most of which signal through the adaptor protein myeloid differentiation factor 88 (MyD88), have been suggested as candidate Aβ innate pattern recognition receptors. It was recently reported that MyD88 deficiency reduced brain amyloid pathology and microglial activation. To assess a putative role of MyD88 in cerebral amyloidosis and glial activation in APPswe/PS1ΔE9 (APP/PS1) mice, we crossed MyD88-deficient (MyD88(-/-)) mice with APP/PS1 mice, interbred first filial offspring, and studied APP/PS1 MyD88(+/+), APP/PS1 MyD88(+/-), and APP/PS1 MyD88(-/-) cohorts. Biochemical analysis of detergent-soluble and detergent-insoluble Aβ1-40 or Aβ1-42 in brain homogenates did not reveal significant between-group differences. Furthermore, no significant differences were observed on amyloid plaque load or soluble fibrillar Aβ by quantitative immunohistochemical analysis. In addition, neither activated microglia nor astrocytes differed among the three groups. These data suggest that MyD88 signaling is dispensable for Aβ-induced glial activation and does not significantly affect the nature or extent of cerebral β-amyloidosis in APP/PS1 mice.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Human ST2 / IL-33R ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
Human IL-12 p70 ELISA Kit, for serum, plasma, cell culture supernatant and urine
Sigma-Aldrich
Mouse IL-12 P40/70 ELISA Kit, for serum, plasma and cell culture supernatant
Sigma-Aldrich
Mouse IL-28A/B ELISA, for serum, plasma and cell culture supernatant