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A recent proteomic study suggested altered mitochondrial function in the cerebrovasculature isolated from deceased cognitively healthy E4 carriers compared to non-E4 carriers, indicating that cerebrovascular bioenergetics may indeed be altered in cognitively healthy E4 carriers (Ojo et al., 2021)
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While there is now little doubt that a degenerative process operates not only in the later progressive phase of the disease, but also likely from the earliest stages of relapsing inflammatory presentations, what is fiercely debated is whether a primary autoimmune inflammation also drives the continuing CNS cytodegeneration and CNS atrophy (Sen et al., 2020
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