Alzheimer’s a tangled web of possible causes


Many of us hear an alarm bell when we forget where we left the keys or see someone we should know but can’t connect the face with a name. Unlike a retired oncologist like me, you won’t try to cover your embarrassment by saying, “I do remember your prostate.”

Fear of losing your memory may have driven you to search articles in the Union-Bulletin, popular journals or the Internet. You might have been advised to try a dozen different approaches. There have been studies that might suggest any of these:

Stop eating two days a week.

Exercise vigorously and frequently.

Become a vegetarian.

Eat Mediterranean style with a fifth of a cup of extra-virgin olive oil in your daily diet.

Sleep eight hours a night.

Reduce blood sugar, regardless of whether you are diabetic.

Get that cholesterol down.

Avoid head trauma risk for your children, and so on.

You may have read about new medicines that may be tomorrow’s magic pill. They have largely targeted the plaques and tangles that Alzheimer described a century ago. It is felt that these misshapen proteins plug up the connections within and between brain cells.

I’ll explain these, but first offer a sad caveat: Two important studies were published involving these medications in the Jan. 24 New England Journal of Medicine, and neither of them showed significant benefit.

More than they feared death, many of my patients feared loss of the ability to control their body functions. Fifty years of caring for cancer patients convinced me that patients with potentially terminal illnesses deserved one-on-one time with a physician, who would help direct them through a maze of tough choices and the sometimes inflated promises of modern technology.

An intelligent and sensitive primary-care doctor once said to me that cancer care was easy. Dr. Phil Siegel told me the tough cases are patients who survive for months and years, unable to keep themselves clean or keep their pain controlled. The hard decisions, he said, involved Alzheimer’s patients.

In next couple of months, I’ll walk you through some of the basic science and the validity of various claims. You might guess that I suspect a link with the concept of a metabolic syndrome.

The prevailing hypothesis is that Alzheimer’s involves the accumulation of a malformed protein or protein-like material. Some authors conclude the disease may start 40 or more years before it is manifested.

I’ll begin with an oversimplified explanation of chemistry you have to understand if you hope to make sense of the claims, the possible interventions and the direction taken by most researchers.

A word of caution: Before thinking about what causes Alzheimer’s, consider what the word causation means. A bacterium causes tuberculosis, but some people are exposed to the organism and don’t become ill. Some diseases only affect children or the elderly. Factors may include immunity, the dose of the bacteria, etc.

Ideally, we will find a link that is common to the disorder and that offers a target of opportunity. Saying that age causes Alzheimer’s doesn’t help, unless the association leads to a cause.

You can’t read much about Alzheimer’s without encountering the term “beta amyloid,” or “amyloid beta,” which I’ll shorten to AB.

Amyloid is a protein compound, or a peptide chain, that is insoluble. The term resulted from a mistaken idea it was a starch. These amyloids are associated with many diseases.

AB is normally found in the body but it is present in large amounts in the brain of Alzheimer patients, and it accumulates in areas critical to memory. Scientists hypothesize that the accumulation of AB plaques may be a cause of the disease, possibly by interfering with transmission of information from neuron to neuron.

We need those connections, of course, to remember where we left our glasses.

Animal studies have been used to investigate the way AB exerts its toxicity. It is important for us to understand the concept but reserve our judgment about whether there is a cause-effect relationship.

One important consideration is whether the underlying problem lies in a mutation, damage in DNA. After all, we know DNA provides a template that determines the kind of proteins a cell makes. We indict oxidants, as agents, which cause mutations, resulting in diseases, like cancer.

Does the same process underlie Alzheimer’s? So far, science has identified apolipoprotein E, or APOE, a gene that is more commonly associated with the disease, and forming abnormal proteins, but it’s not present in all patients.

Alois Alzheimer, a German neuropathologist, described AB as well as protein tangles that formed inside brain cells.

As I noted above, much of the effort to date has assumed that blocking the formation of plaques and tangles might combat the disease or its progression.

The articles in the New England Journal of Medicine don’t look encouraging for an imminent breakthrough. I hope I’m wrong. There’s a related problem — aging brains suffer from vascular disease that reduce oxygen and nutrients to the brain.

As usual, I’m running out of space. Next month, I’ll run through some of the things we might do now. Some are in the list above, but it excludes some important ones.

Does keeping your brain active make a difference? That will be a good starting point.

Dr. Larry Mulkerin is a retired clinical professor and oncologist who lives in Walla Walla. A former U.S. Army Green Berets medical officer with experience in the Middle East, he also is the author of “The Ayatollah’s Suitcase,” a novel available at and other online book retailers. He can be reached at


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