IFN-γ production by amyloid β-specific Th1 cells promotes microglial activation and increases plaque burden in a mouse model of Alzheimer's disease.

Browne TC, McQuillan K, McManus RM, O'Reilly JA, Mills KH, Lynch MA.
Journal   J Immunol
Species  
Analytes Measured   Abeta 38 , Abeta 40 , Abeta 42
Matrix Tested   Brain homogenates
Year   2013
Volume   190
Page Numbers   2241-2251
Application   Alzheimers
Abstract
Alzheimer's disease (AD) is characterized by the presence of amyloid-β (Aβ)-containing plaques, neurofibrillary tangles, and neuronal loss in the brain. Inflammatory changes, typified by activated microglia, particularly adjacent to Aβ plaques, are also a characteristic of the disease, but it is unclear whether these contribute to the pathogenesis of AD or are a consequence of the progressive neurodegenerative processes. Furthermore, the factors that drive the inflammation and neurodegeneration remain poorly understood. CNS-infiltrating T cells play a pivotal role in the pathogenesis of multiple sclerosis, but their role in the progression of AD is still unclear. In this study, we examined the role of Aβ-specific T cells on Aβ accumulation in transgenic mice that overexpress amyloid precursor protein and presenilin 1 (APP/PS1). We found significant infiltration of T cells in the brains of APP/PS1 mice, and a proportion of these cells secreted IFN-γ or IL-17. Aβ-specific CD4 T cells generated by immunization with Aβ and a TLR agonist and polarized in vitro to Th1-, Th2-, or IL-17-producing CD4(+) T cells, were adoptively transferred to APP/PS1 mice at 6 to 7 mo of age. Assessment of animals 5 wk later revealed that Th1 cells, but not Th2 or IL-17-producing CD4(+) T cells, increased microglial activation and Aβ deposition, and that these changes were associated with impaired cognitive function. The effects of Th1 cells were attenuated by treatment of the APP/PS1 mice with an anti-IFN-γ Ab. Our study suggests that release of IFN-γ from infiltrating Th1 cells significantly accelerates markers of diseases in an animal model of AD.

View Publications

Related Products

R-PLEX Human Aβ42 (6E10) Antibody Set
Aβ42 (6E10) | Human
Singleplex
NEW
R-PLEX Human Aβ40 (6E10) Antibody Set
Aβ40 (6E10) | Human
Singleplex
NEW
Human (6E10) Aβ38 Ultra-Sensitive Kit
Aβ38 | Human
Singleplex
Human (6E10) Aβ40 Ultra-Sensitive Kit
Aβ40 | Human
Singleplex
Human (6E10) Aβ42 Ultra-Sensitive Kit
Aβ42 | Human
Singleplex
V-PLEX Human Aβ42 Kit
Aβ42 | Human
Singleplex
V-PLEX Aβ Peptide Panel 1 (4G8) Kit
Aβ38, Aβ40, Aβ42 | Human, Mouse, Rat
Multiplex
V-PLEX Aβ Peptide Panel 1 (6E10) Kit
Aβ38, Aβ40, Aβ42 | Human
Multiplex
V-PLEX Aβ40 Peptide (4G8) Kit
Aβ40 | Human, Mouse, Rat
Singleplex
V-PLEX Aβ40 Peptide (6E10) Kit
Aβ40 | Human
Singleplex
V-PLEX Aβ42 Peptide (4G8) Kit
Aβ42 | Human, Mouse, Rat
Singleplex
V-PLEX Plus Aβ Peptide Panel 1 (4G8) Kit
Aβ38, Aβ40, Aβ42 | Human, Mouse, Rat
Multiplex
V-PLEX Plus Aβ Peptide Panel 1 (6E10) Kit
Aβ38, Aβ40, Aβ42 | Human
Multiplex
V-PLEX Plus Aβ40 Peptide (4G8) Kit
Aβ40 | Human, Mouse, Rat
Singleplex
V-PLEX Plus Aβ40 Peptide (6E10) Kit
Aβ40 | Human
Singleplex
V-PLEX Plus Aβ42 Peptide (4G8) Kit
Aβ42 | Human, Mouse, Rat
Singleplex
V-PLEX Plus Human Aβ42 Kit
Aβ42 | Human
Singleplex
Neurodegeneration Control Pack 1
Aβ38, Aβ40, Aβ42, Tau (total) | Human, Mouse, Rat
V-PLEX Aβ38 Peptide (4G8) Kit
Aβ38 | Human, Mouse, Rat
Singleplex
V-PLEX Aβ38 Peptide (6E10) Kit
Aβ38 | Human
Singleplex
V-PLEX Plus Aβ38 Peptide (4G8) Kit
Aβ38 | Human, Mouse, Rat
Singleplex
V-PLEX Plus Aβ38 Peptide (6E10) Kit
Aβ38 | Human
Singleplex
Browse Our Products

By Analytes
By Applications
Search
Customer Service/Orders


Scientific/Technical Support


Instrument Support


Company Headquarters