So what does the ApoE4 gene do that's so bad?

If you ask 23andMe to test your genome for AD risk, they will look first for the ApoE4 variant of the gene that codes for the apolipoprotein E protein.  There are three variants (alleles) of the gene for this protein, ApoE2, ApoE3, and ApoE4.  Cells use information encoded in the gene to construct this protein.  

The function of the apolipoprotein E protein is to, among other things, transport cholesterol through the blood, but the ApoE4 variant can cause problems on several fronts.  In Beating the Dementia Monster, we said that it could cause inflammation in the brain, and that could be part of how the AD disease process begins and progresses.

It turns out that's not all it does to cause problems.  This week's issue of ALZForum carried an interesting article on ApoE4, treating it like a criminal with a bad rap sheet.  The article highlighted several "criminal charges" regarding ways in which the protein contributes to the advent and development of AD.  The article got a little deep, but here are some takeaways.

• It acts on microglia cells to inhibit them from doing their job.  The microglia are the brain's immune system, and they help remove dead cells and waste from the brain.  The accumulation of debris in the brain is a characteristic of AD.  In fact, there's quite a bit of attention in AD research on ways in which microglia are inhibited. 
• It causes vascular problems in the brain, such as by making blood vessels leaky and breaching the blood-brain barrier.  "What's good for the heart is good for the brain," so what's bad for the cardiovascular system is bad for the brain. 
• It impairs axonal plasticity or the ability of nerve cells to make certain kinds of repairs.

 And there was more.  Quite the list!