Apolipoprotein E and cognitive performance

Key proteins implicated in the development of Alzheimer's disease are the β-amyloid precursor protein, which gives rise to the β-amyloid peptides that accumulate in the deteriorating brain1,2, and the different isoforms of apolipoprotein E (apoE). The apoE4 variant increases the risk of developing the disease compared with apoE3 (ref. 3). We have tested the spatial memory of transgenic mice carrying human forms of these proteins and find that it is impaired in mice with apoE4 but not those with apoE3, even though the levels of β-amyloid in their brains are comparable. The fact that apoE3, but not apoE4, can protect against cognitive deficits induced by β-amyloid may explain why human apoE4 carriers are at greater risk of developing Alzheimer's than apoE3 carriers.