Developments in Alzheimer's Disease

There's yet more AD-related research out today, this time in Neuron2, and that work expands our understanding of why apolipoprotein E (ApoE) is involved in the Alzheimer's disease. ApoE is a component of LDL and VLDL, the types of cholesterol-containing lipoproteins that cause heart disease. But research has also shown that people who carry one of the ApoE polymorphisms, ApoE4, have a greatly increased risk for developing AD later in life. As with cholesterol, where ApoE is involved in clearance of the LDL and VLDL particles, ApoE also binds to Aβ and aids its removal by specialized cells in the brain called microglia.

In this study, microglia from ApoE knockout mice were incubated with Aβ, which they were unable to degrade nearly as effectively as microglia from wild-type mice. When the experiment was repeated along with the addition of different isoforms of human ApoE, it was discovered that ApoE2, and -E3 all conferred back the ability to degrade Aβ, but ApoE4 was significantly less effective. The researchers also showed that the lipidation state of ApoE (how many lipids were bound to the molecule) was important in how effective the degradation of Aβ was, with greater lipidation resulting in greater degradation. Since we have drugs that can increase this lipidation state, it suggests another possible drug target for treating AD.

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