Apolipoprotein E facilitates neuritic and cerebrovascular plaque formationin an Alzheimer's disease model

The epsilon 4 allele of apolipoprotein E (ApoE) is an important genetic ris k factor for Alzheimer's disease (AD). Increasing evidence suggests that th is association may be linked to the ability of ApoE to interact with the am yloid-beta (A beta) peptide and influence its concentration and structure. To determine the effect of ApoE on A beta and other AD pathology in vivo, w e used APPsw transgenic mice and ApoE knockout (-/-) mice to generate APPsw animals that carried two (ApoE +/+), one (ApoE +/-), or no copies (ApoE -/ -) of the normal mouse ApoE gene. At 12 months of age, A beta deposition wa s present in the cortex and hippocampus and was also prominent within lepto meningeal and cortical blood vessels of all APPsw ApoE +/+ mice. Importantl y, although A beta deposition still occurred in APPsw ApoE -/- mice, no fib rillar A beta deposits were detected in the brain parenchyma or cerebrovasc ulature. There was also no neuritic degeneration associated with A beta dep osition in the absence of ApoE. These data demonstrate that ApoE facilitate s the formation of both neuritic and cerebrovascular plaques, which are pat hological hallmarks of AD and cerebral amyloid angiopathy.