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Early Stage LPS Injection Causes Long-term Effects on Microglial Heterogeneity in Alzheimer's Mouse Model

Zeng, Hairuo (2023) BINP51 20222
Degree Projects in Bioinformatics
Popular Abstract
Alzheimer's disease is a neurodegenerative disease that often affects the elderly and is accompanied by cognitive loss. The disease is characterized by the formation of amyloid beta (Aβ) plaques and Tau tangles in the brain, and microglia, the brain's resident immune cells, have been found to play a critical role in the progression of the disease. Recent studies suggest that microglia may exhibit innate immune memory, which could be involved in the pathogenesis of Alzheimer's disease.

A new study aimed to investigate whether postnatal inflammation could imprint microglia with this innate memory and how this might affect Alzheimer's disease pathology. The researchers injected wildtype (WT) and Alzheimer's disease model mice with LPS (a... (More)
Alzheimer's disease is a neurodegenerative disease that often affects the elderly and is accompanied by cognitive loss. The disease is characterized by the formation of amyloid beta (Aβ) plaques and Tau tangles in the brain, and microglia, the brain's resident immune cells, have been found to play a critical role in the progression of the disease. Recent studies suggest that microglia may exhibit innate immune memory, which could be involved in the pathogenesis of Alzheimer's disease.

A new study aimed to investigate whether postnatal inflammation could imprint microglia with this innate memory and how this might affect Alzheimer's disease pathology. The researchers injected wildtype (WT) and Alzheimer's disease model mice with LPS (a bacterial endotoxin) at a postnatal stage before the formation of the blood-brain barrier. They performed single-cell RNA sequencing on fresh microglia 6 months after the injection to look at the effects on microglia heterogeneity.

The study revealed that long-term effects of LPS led to a subtle decrease in the expression levels of homeostatic genes, but significant changes in terms of transcriptional factors. Interestingly, the researchers identified a unique cluster of microglia enriched with higher expression levels of certain genes, which vanished in LPS-injected Alzheimer's disease model mice. This unique cluster was found to be under cell division and distinct from other microglia subclusters. The findings provide new insights into the mechanisms underlying microglial innate immune memory and suggest a potential time-window for pharmacological therapy in Alzheimer's disease. (Less)
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author
Zeng, Hairuo
supervisor
organization
course
BINP51 20222
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9122459
date added to LUP
2023-06-09 11:42:14
date last changed
2023-06-09 11:42:14
@misc{9122459,
  author       = {{Zeng, Hairuo}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Early Stage LPS Injection Causes Long-term Effects on Microglial Heterogeneity in Alzheimer's Mouse Model}},
  year         = {{2023}},
}