APOEε4 triggers early microglial activation in Alzheimer’s disease

Microglial activation plays a key role in the accumulation of Alzheimer’s disease (AD) proteins such as amyloid and tau. Previously, microglial reactivity has been shown to be triggered by amyloid beta, but João Pedro Ferrari-Souza, MD-PhD student, University of Pittsburgh, Pittsburgh, PA, explains that microglial reactivity can also occur independently of amyloid beta in early disease progression. Based on evidence in animal models implicating APOEε4 in microglial activation, the team undertook a study in 118 participants with normal cognition, mild cognitive impairment, or AD to further investigate this relationship. Participants underwent PET imaging for tau tangles, amyloid beta, and microglial activation. The study found that APOEε4 is associated with increased microglial activation in early Braak regions within the medial temporal cortex, independent of amyloid beta and tau pathologies. This thus suggests APOEε4’s involvement in triggering early microglial activation in early AD. This interview took place at the AD/PD™ 2023 congress in Gothenburg, Sweden.

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