Abstract
AbstractBackgroundThe strongest genetic risk factor for developing late‐onset Alzheimer’s disease (AD), ApoE4, drives inflammation in the central immune system. However, it remains largely unkown whether ApoE4 also affects the adaptive immune response.MethodFirst, we performed mass cytometry to identify an immune signature in splenocytes of human ApoE4‐TR and ApoE3‐TR mice. Following this, we used immunohistochemistry to check for brain infiltration of immune cells and BBB integrity.ResultWe identified an adaptive immune response in splenocytes of human ApoE4‐TR mice displayed by a shift from naïve and effector to memory CD8+ T cells. Futhermore, we found an increased number of CD8+ T cells in the brain of ApoE4‐TR mice. ApoE4 also has an effect on BBB integrity, as indicated by a decrease in the tight junction proteins, VE‐cadherin and claudin‐5, in ApoE4‐TR mice compared to ApoE3‐TR mice.ConclusionApoE4 induces an adaptive immune response in mouse splenocytes resulting in brain infiltration of CD8+ T cells.
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