APOE and Alzheimer disease: Our establishment of a direct relationship between inheritance of APOEε4 alleles and a dramatic reduction in transcript levels for three mRNAs that encode proteins required for lysosomal autophagy in brain tissue from AD carriers of APOEε4,4 but not APOEε3,34 suggests a need for a targeted drug to counteract the effect of ApoE4 on lysosomal autophagy.