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Neuroinflammation in Alzheimer's Disease Contributes to A2-type Reactive Astrocytic Profile in iPSC Derived Patient Astrocytes

  • Author(s): Hui, Lauren Tin-Yan
  • Advisor(s): Gage, Fred H
  • et al.
No data is associated with this publication.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by loss of neurons and synapses throughout the brain. Increased neuroinflammation has been observed in the brains of AD patients and is hypothesized to play a role in the pathology of the disease. Inflammation in the brain is thought to be primarily initiated by the non-neuronal cells of the brain, glia cells. One type of glia, astrocytes, are suspected to play a role in the onset and progression of AD through inflammation. Recent characterization of reactive astrocytes has identified two activated astrocyte states: a harmful, pro-inflammatory A1 state or a helpful, anti-inflammatory A2 state when exposed to CNS injury. In this thesis, I asked if A1 or A2 astrocyte states were different between AD and control astrocytes. Here, I analyzed RNA-sequencing data from AD astrocytes generated from patient-derived induced pluripotent stem cells (iPSCs) along with age-matched controls to identify the relative proportions of A1 and A2 states. Surprisingly, I found that AD astrocytes have an increase in A2-type, “helpful” astrocytes relative to age-matched cognitively normal controls. These results reflect the complexity of AD and suggest new ways of thinking about inflammation in AD.

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This item is under embargo until April 12, 2023.