This is another installment in my response to MScarabagg@aol.com who asked last fall whether ALS, Parkinson's, Alzheimer's and autism might be related. In this post, I will discuss evidence that a blood protein known as apoE may explain why some people (and some families) are more vulnerable to developing ALS and other diseases of the central nervous system (CNS) as a result of exposure to mercury.

In previous posts, I have reviewed a portion (in some cases, a very small portion) of the evidence supporting the following statements:

1. human exposure to mercury in the industrialized world has risen by six- to eight-fold since the early 1800s due to the invention of silver-mercury fillings (amalgam) around 1820, and to the increase in mercury in the air and water caused by the Industrial Revolution;
2. people with amalgam fillings have two to three times as much mercury in their bodies as people without amalgams;
3. mercury may cause ALS, Parkinson's disease (PD), and Alzheimer's disease (AD). Note: At no time have I said mercury is the only cause of these diseases, nor have I said that mercury is implicated in 100 percent of all cases of these diseases.

In 1993, the first study linking a particular type of apolipoprotein E (apoE) to AD was published. Since then, a flood of studies have confirmed that apoE plays a role in AD. In the last two or three years, investigators have begun to inquire whether apoE might also play a role in PD, ALS, MS, and other diseases of the CNS. At this point, the literature on apoE is voluminous and evolving rapidly.

Apolipoprotein E (apoE) is a protein which transports cholesterol in the bloodstream. In humans, this protein comes in three varieties: 2, 3 and 4. It is well established now that people with the apoE4 variety of this protein are more likely to develop AD, people with apoE2 are least likely, and people with apoE3 have an intermediate risk.

Several hypotheses have been advanced to explain why apoE2 is protective against AD while apoE3 is less so and apoE4 is even less protective. One hypothesis consistent with the assertion that mercury often plays a role in AD is based upon the difference in the amino acids that make up apoE2, 3, and 4. Like all proteins, apolipoprotein consists of chains of amino acids. ApoE2 -- the protective form of apoE -- has two amino acids called cysteines in its amino-acid chain, apoE3 has one cysteine, and apoE4 has none. Arginine, another amino acid, replaces one cysteine in apoE3 and both cysteines in apoE4. Arginine does not contain sulfur while cysteine does. Mercury loves sulfur. In the presence of sulfur, mercury will unbind from virtually any other substance in order to bind with sulfur. For this reason, sulfur is a member of a class of substances called 'mercaptans,' which, I believe, is Latin for "mercury capture."

ApoE2 is therefore a better scavenger of mercury than apoE3, and apoE3 is even better than apoE4. In other words, regardless of your exposure level to mercury, you probably retain less mercury in your body if you were born with the genes that give you apoE2 or 3. In short, this hypothesis asserts that people with the apoE2 or 3 variety are less likely to get AD because their blood does a better job of ridding the body of mercury and preventing a buildup in body tissue, including the CNS.

If this "apoE-sulphur" hypothesis is correct, and if mercury also plays a role in ALS, PD, and MS, which I suspect it does, then one would expect to find that apoE 2 and 3 play a protective role in these other diseases of the CNS. The evidence linking apoE status to diseases other than AD is nowhere near as strong, but it is there. In my next post, I will review this evidence.

Kip Sullivan