THE CAUSES OF ALZHEIMER’S DEMENTIA ARE CONFUSING

Alzheimer’s-related dementia is a serious concern to both the general public and medical researchers. Anyone who has been involved in the care of a patient with Alzheimer’s dementia knows the degree to which this disorder affects family, interpersonal communication, and relationships. As adults live longer, memory care facilities are opening all over the country to accommodate the increasing number of people with dementia.

As I see it, other than the obvious effect Alzheimer’s has on social inaction, two very important pieces are missing from the Alzheimer’s puzzle. From a scientific viewpoint they are:

One: To date, the specific molecular-level cause of Alzheimer’s is uncertain.

Two: To date, no drug has been developed that demonstrates efficacy by interrupting the progression of the disease or improving cognition.

Thus, since the specific pathologic cause of Alzheimer’s dementia has not been determined, a treatment that modifies or stops that abnormality has not been developed. In other words, since researchers don’t know what causes dementia, they are unable to design a treatment that will help. As of now, two theories are the accepted opinions for what occurs at the cellular and molecular levels, but they are only educated conjecture. These two theories are:

The Cholinergic Hypothesis: Acetylcholine, ACh, is a chemical messenger (also called a neurotransmitter). ACh makes the nerves work by carrying nerve impulses from one nerve to another. It is a chemical bridge that carries an impulse from the nerve where it originates (pre-synaptic neuron) to the nerve where it performs a function (post-synaptic neuron). The theory says something interrupts ACh from performing its messenger function. When this occurs in the muscles of the extremities, the result is Myasthenia Gravis (MG—severe muscle weakness, drooping eyelids, trouble walking, etc.) In the brain, “ACh is involved in several physiological processes including memory, attention, sensory information, learning, and other critical functions.” Any interference with ACh in the brain causes dementia-like symptoms. In Alzheimer’s, degeneration of the neurons containing ACh has been shown to occur. The theory results in 3 possibilities: one—ACh production is decreased, two—the cells that receive ACh don’t work properly, three—something neutralizes ACh.

The Amyloid Hypothesis: In the brains of dementia patients, there is an abnormal collection of a protein substance called Beta Amyloid (BA). BA is found in normal brains, too. The theory is that in Alzheimer’s, BA slowly degrades, and the chemical residue left behind is toxic to brain cells. The residue (peptides) produces Tau proteins and leads to brain cell death. 

It’s easy to see how complicated this problem is. Studying the brain at a microscopic level in a patient who is still alive is very difficult. Most study is done by using non-invasive testing methods or by exam at autopsy. That proves to be a disadvantage. Drug researchers quest for effective drug therapy faces the similar challenges. Besides all of that, researchers aren’t certain that dementia is caused by these pathologies. They remain hypotheses (theories). 

Like many things in medicine, discoveries or breakthroughs can come as accidents or unexpected surprises. These two “theories” may be all wrong, and in the future, someone may stumble upon a plausible explanation no one thought about. Those things happen often. I certainly hope an explanation does come someday just as I hope there is a discovery that cures cancer. However, just like stopping people from aging, these discoveries may never come. Living forever on earth sounds cool, but do we really want to live that long? I don’t think so.

References: Breijyeh Z, Karaman R. Comprehensive Review on Alzheimer’s: Causes and Treatment. Molecules 2020 Dec;25(24):5789.