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AD/PD 2023 | APOEε4 drives tau accumulation through Aβ-dependent and Aβ-independent pathways

João Pedro Ferrari-Souza, MD-PhD student, University of Pittsburgh, Pittsburgh, PA, comments on the relationship between the APOEε4 allele, amyloid beta (Aβ) pathology, and tau tangle accumulation. In a recent study, Mr Ferrari-Souza identified APOEε4 is a key factor in the Aβ-dependent formation of tau tangles through tau hyperphosphorylation. The presence of the APOE4 allele in combination with Aβ resulted in significantly higher tau accumulation rates, compared to individuals only positive for Aβ or APOEε4. However, the team have also noted Aβ-independent effects of APOEε4 on downstream tau accumulation, mediated by microglia activation. PET imaging of 118 participants with normal cognitive, mild cognitive impairment, or Alzheimer’s disease found APOEε4 to be associated with increased microglial activation in early Braak regions within the medial temporal cortex, independent of Aβ. This interview took place at the AD/PD™ 2023 congress in Gothenburg, Sweden.

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