The observed association between astrocyte–plaque coverage and both increased plaque circularity and reduced dystrophic neurites suggests that it is a beneficial function impaired in the context of APOE4. In line with this perspective, Mathur and colleagues observed that astrocyte interactions with plaque subtypes in AD brain were related to reduced cognitive impairment, including the finding of decreased astrocyte interactions with compact plaques predicting lower cognitive ability in a manner that was deleteriously affected by APOE4 [29]. Here, APOE is linked to Cognitive impairment.