Modulation of Aβ deposition in APP transgenic mice by an apolipoprotein E null background

Several lines of evidence implicate apolipoprotein E (apoE) and its receptor - the low density lipoprotein receptor related protein (LRP) - in Alzheimer's disease (AD) pathogenesis, including increased amyloid deposition in human AD brains of people containing the apoE ε4 allele, presence of apoE and LRP in amyloid plaques, and in vitro uptake of amyloid precursor protein (APP) and amyloid β protein (Aβ) by LRP. Studies of crosses of apoE knockout mice with APP transgenic mice support a complex interaction between apoE and Aβ deposition. In the Tg2576 mice expressing human APP_K670N-M671L, apoE determines the amount, morphology, vascular pattern, and neuropil response to Aβ deposits. In the PDAPP mice expressing human APP_V717F, apoE also affects the anatomical localization of cerebral Aβ deposits. Thus, APP transgenic mice can serve as models to investigate genetic influences on the amount and timing of cerebral amyloidosis, the morphology of amyloid plaques, and the vulnerability of specific neuroanatomical regions to Aβ deposition.