APP and Alzheimer disease: Apolipoprotein E4 in the pathogenesis of AD related to beta-amyloid plaques: in vivo, ApoE is associated with amyloid plaques, and in vitro, free ApoE3 and ApoE4 can form stable complexes with beta-amyloid plaques with ApoE4 binding more quickly and firmly than ApoE3.(78) There are reports of mechanisms in ApoE-deficient rats expressing the humanized amyloid precursor protein (hAPP) through a mutation, showing that ApoE is necessary to form fibrillar amyloid plaques.