Extended Data Fig. 9: Putative pathway by which ApoE4 in BAM induces vascular oxidative stress, neurovascular dysfunction and enhanced white matter injury.

(1) ApoE4 in BAM acts on ApoE receptors, for example, LRP1 as a candidate receptor, to increase intracellular Ca2+ in BAM in a cell autonomous manner resulting in NOX activation, (2) vascular oxidative stress, and (3) neurovascular dysfunction and reduced cerebral perfusion, which, in turn, leads to (4) enhanced white matter damage and cognitive impairment.