THESIS
2018
viii, 41 pages : color illustrations ; 30 cm
Abstract
Alzheimer’s disease (AD) is the most common form of dementia with no effective
treatment nowadays. Emerging evidences suggest that microglia, the major type of
immune cell in central nervous system, may contribute to AD pathogenesis.
Subpopulation of microglia adopted a disease-associated/reactive state and skews away
from homeostatic state along AD progression. While the disease-associated microglia
(DAM) are co-localised with amyloid plaques, it remains unclear how the DAM
subpopulation contribute to AD pathogenesis. We previously demonstrated that
interleukin 33 (IL-33) administration rescues impaired cognitive functions and pathology
in an AD transgenic mouse model, in part through enhancing amyloid phagocytosis by
microglia. Here, we report that IL-33 administration regula...[
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Alzheimer’s disease (AD) is the most common form of dementia with no effective
treatment nowadays. Emerging evidences suggest that microglia, the major type of
immune cell in central nervous system, may contribute to AD pathogenesis.
Subpopulation of microglia adopted a disease-associated/reactive state and skews away
from homeostatic state along AD progression. While the disease-associated microglia
(DAM) are co-localised with amyloid plaques, it remains unclear how the DAM
subpopulation contribute to AD pathogenesis. We previously demonstrated that
interleukin 33 (IL-33) administration rescues impaired cognitive functions and pathology
in an AD transgenic mouse model, in part through enhancing amyloid phagocytosis by
microglia. Here, we report that IL-33 administration regulates the gene signature of
microglia in AD transgenic mice using single-cell RNA sequencing. While IL-33
administration did not significantly affect the proportion of homeostatic microglia in
APP/PS1 mice, it modulates the transcriptome signature of DAM. Thus, our results
collectively suggest that the transition of microglial state may play a role in mediating the
beneficial effects of IL-33 in AD.
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