Alzheimer’s: Its causes, current treatment, and potentially promising research

Alzheimer’s Disease is the most common cause of dementia.

While it usually strikes older people, it can be seen in younger age groups as well.

Alzheimer’s causes several problems with cerebral functioning: memory loss, difficulty storing new memories, problems with language functions, depression, hallucinations, and problems with using mathematical functions, among others.

Alzheimer’s is progressive and leads to death about 5-10 years after diagnosis. Death usually occurs from disease-related causes (like pneumonia, cachexia, vascular diseases, etc.). Alzheimer’s may be the 5th or 6th leading cause of death in the US today.

Patients with Alzheimer’s develop an excessive amount of β-amyloid and tau protein in their brains. β-Amyloid forms the plaques that interfere with nerve signal transmission, among other things, and can be toxic to the nearby neurons. Tau protein acts to cause neurons to form neurofibrillary tangles and it too, is toxic to nerve cells. The areas of the brain most affected cause the results that are seen in the disease: memory loss, computational problems, etc.

What causes Alzheimer’s?

There IS a genetic component. The gene that contributes to the production of the plaques is found on chromosome 21. People with Down’s syndrome (Trisomy 21) have three copies of chromosome 21 and they produce about 2 times as much of this precursor that leads to the plaques which are a part of AD. They develop Alzheimer’s at an early age.

There are other genes on other chromosomes involved in the pathogenesis of AD, too. But genetics seems to only be part of the cause. Immune mechanisms seem to have a part to play, as do free radicals, diabetes, homocysteine, trauma to the brain and possibly other factors.

Alzheimer’s treatment

Treatment includes any of several drugs that may somewhat slow the progression of Alzheimer’s for a brief time but are unable to stop it.

Elderly Patient via Shutterstock

Elderly Patient via Shutterstock

One class of drugs are cholinesterase inhibitors. These inhibit the enzyme that breaks down acetylcholine (ACh), and allows more ACh to remain available to the neurons. As Alzheimer’s progresses, the amount of acetylcholine produced by the brain decreases. And ACh is important for proper memory function. As the enzyme that breaks down ACh gets blocked, ACh levels rise.

A different type of medication is also available, this one is an N-methyl D-aspartate (NMDA) antagonist. NMDA works by decreasing the amount of available glutamate in the brain. Higher than normal levels of glutamate can cause brain cell death.

Regrettably, these drugs, even when used in combination, only delay the inevitable. Perhaps they will allow the patient to be able to continue to be able to use the bathroom on his own for several more months. It makes things a little easier on the patient and family, and helps the patient maintain some dignity.

New Alzheimer’s treatments on the horizon

However, there is some interesting information available, including a new treatment in clinical trials.

First is a vaccine. Researchers found several years ago that in mice models of Alzheimer’s, immunologically stimulating the mice by using fragments of proteins found in Alzheimer’s caused improvements in memory, reduced inflammation, may have healed and/or caused new neurons to form and helped clear away plaque deposits.

Glatiramer, a drug that is given to patients with multiple sclerosis, seemed to produce similar results. Glatiramer is now just starting human trials in patients with Alzheimer’s. So the possibility exists that this immunomodulatory drug may do more than just slow the inevitable course of the disease. Groups of patients are now starting to receive the drug via injection, and they will be carefully observed to see if cognitive function improves and if plaques diminish.

A vaccine was also developed and clinical trials were begun. But there were side effects from the vaccine that caused the trial to be ended. Research continues on how to make a vaccine that would avoid those complications. But that did, indirectly, lead to another therapy under study. Researchers intravenously infused pre-made anti-amyloid antibodies into Alzheimer’s patients. Research with this technique is continuing.

In a paper just published this month, a research team has found that the areas of the brain most compromised by beta amyloid and tau protein also have a much higher level of iron in those areas. Alzheimer’s preferentially attacks certain areas of the brain, like the hippocampus early in the disease and spares others, like the thalamus, until later.

In the brains studied, the hippocampus’ iron levels were substantially higher that iron levels in the thalamus. This will lead to further research and may provide some additional potential treatment for Alzheimer’s. Though that would be years away.

So, while current therapy for Alzheimer’s Disease is only able to temporarily slow its progression, there are some drug studies in progress of therapies that may be able to do much more.

Mark Thoma, MD, is a physician who did his residency in internal medicine. Mark has a long history of social activism, and was an early technogeek, and science junkie, after evolving through his nerd phase. Favorite quote: “The most exciting phrase to hear in science... is not 'Eureka!' (I found it!) but 'That's funny.'” - Isaac Asimov

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