Recently, single-nucleus RNA sequencing studies have identified an enrichment of LD-rich microglia in ApoE 4/4 AD brains [153], linking ApoE, particularly the ApoE4 isoform, to the alteration of microglial metabolism by disrupting multiple metabolic pathways, leading to impaired immune responses and the exacerbation of AD pathology [154, 155]. Here, APOE is linked to Alzheimer disease.