What's so bad about ApoE4?

The well-known genetic factor in AD is the presence of the ApoeE4 variant of the ApoE gene.  If a genetic testing service tells you that your DNA carries this gene variant, it doesn't mean that you will get AD.  You are, however, at higher risk.  There are other things that can trigger the onset of the disease.  I do not carry the gene, but I have developed AD.

But what does the gene variant do, and why is the ApoE4 gene a factor in development of AD?

There was an interesting article that discussed this in this week's issue of ALZForum.  The article was generally about different proteins and their genes that affect AD, and ApoE was one of them.  It discussed specifically the generation of new neurons in the hippocampus, which is where physical exercise comes in to fight AD.  (Recall from Beating the Dementia Monster that physical exercise promotes the production of "brain-derived neurotropic factor" which promotes the generation of new brain cells.  The generation of new brain cells occurs primarily in the hippocampus.)

At least with respect to the ApoE gene, research found that presence of proteins from the most common gene variant (ApoE3) supports the growth and branching of dendrites in new neurons.  The ApoE4 proteins do not do this and therefore do not support the factors that improve the hippocampus and cognitive performance. 

I thought this was very interesting.