In contrast, APOE4 competitively binds to CLEAR motif and suppresses the binding of TFEB, resulting in decreased transcriptional expression of multiple TFEB target genes such as LC3, SQSTM1, and LAMP2 [94] (Fig. 3A).These results highlight the critical roles of a key AD risk gene APOE4 in the modification of TFEB activities. This evidence concerns the gene SQSTM1 and Alzheimer disease.