Alzhiemer’s Causes and Risk Factors


The brain is a complex signaling system much a like a computer. There’s information coming in, information being processed and turned into memories, and information going out. All of this is accomplished in the brain by means of hundreds of billions of nerve cells, each capable of branching out and connecting with hundreds of thousands of other nerve cells. Unlike pieces of wiring in a computer, however, nerve cells don’t touch each other. Instead, they use dozens of chemical messengers to communicate across tiny gaps called synapses. Somewhere, somehow, something goes wrong and causes Alzheimer’s. Researchers still have not identified exactly what that something is.

How does Alzheimer’s destroy the brain?
Learn about various theories about the structural changes in the brain may lead to degeneration.

Searching for causes
Find out how proteins, the genes, chemical messengers, metabolism of glucose, calcium and the environment may provide clues.

Risk factors
Know the odds. Well-established factors such as advanced age, family history, being female and environmental influences may increase the chances. Discover probable factors that you should also be aware of.

Not one cause but many?
How far are we toward understanding cause or interaction of causes of the disease?

How does Alzheimer’s destroy the brain?

Alzheimer’s disease or at least age-related memory loss has been around for a long time. Historical texts from ancient Egypt, Greece and Rome describe symptoms similar to those of Alzheimer’s, and Shakespeare wrote about old age as being a time of “second childishness and mere oblivion.” But it wasn’t until 1906 that a German doctor named Alois Alzheimer characterized the structural changes in the brains of people with what became known as Alzheimer’s disease.

At that time, Dr. Alzheimer had been treating a woman with an unusual memory loss for several years. She could name objects shown to her but would immediately forget them. She often didn’t know what the objects were for. The woman forgot or misused words. She described her condition by saying, “I have lost myself.” When the woman died at age 56, Dr. Alzheimer performed a brain autopsy and discovered the two physical features that still are used to definitively diagnose Alzheimer’s after a person dies.

He noticed inside nerve cells in the cerebral cortex (the part of the brain responsible for reasoning and memory) were bundles of twisted strands that he called neurofibrillary tangles. He also observed that around the nerve cells were dense deposits or senile plaques. Dr. Alzheimer speculated the nerve tangles and plaques caused the woman’s dementia, but he couldn’t be sure they were the cause and not the result of the disease.

Today, scientists are still not sure. They know tangles and plaques develop only in the parts of the brain that control memory and knowledge and that as they form, the nerve cells become so disorganized that they stop functioning and eventually die. All the activities those cells control die with them. Researchers also know the tangles are associated with an abnormal accumulation of a protein called tau and plaques are made of a core of a peptide, called beta-amyloid-42, around which is clumped debris from broken-down cells. A peptide is a fragment of a protein molecule.

Searching for causes

  • The proteins: In a healthy nerve cell, tau forms part of the structural scaffolding of the cell that helps distribute nutrients. In a cell affected by Alzheimer’s, something causes the tau molecules to twist, collapsing the scaffolding and killing the cell. Beta-amyloid is also normally found in healthy individuals, but something makes it accumulate abnormally in Alzheimer’s patients. One suggestion is that some other substance binds to beta-amyloid, making it come out of solution and get deposited as plaques. Another suggestion is that the peptide is toxic to nerve cells. This idea is supported by a study in which brain cells died when beta-amyloid was added to the cell culture. Why it’s toxic is unclear. It may allow too much calcium into the nerve cell, which can be lethal, or reduce the amount of a substance needed to make a necessary chemical messenger. Or, it may be the body’s own defense against the plaques that cause the damage. The plaques trigger an immune response that leads to inflammation, which in turn robs brain cells of nutrients and oxygen. Recently, non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, were shown to slow the progress of the disease.
  • The genes: Studies done on families with many cases of Alzheimer’s occurring late in life have implicated a gene on chromosome 19. The gene codes for a protein called apolipoproteinE or ApoE that can bind to beta-amyloid. Once researchers discovered 40 percent of Alzheimer’s patients had an unusual form of the protein called ApoE4, they began to suspect that it may latch onto beta-amyloid and make it more likely to form plaques. It may also be the reason why the tau protein twists inside cells. Other theories say it’s the reason why nerve cells affected by Alzheimer’s have shorter branches that reach out to and communicate with other cells. However, because not everyone with the gene for ApoE4 develops Alzheimer’s and not everyone with Alzheimer’s has the gene, it cannot be the only cause. Other genes on other chromosomes have also been implicated. For example, research on families in which some members develop the disease early in life has turned up a gene on chromosome 21. This gene directs the production of a mutated version of the protein that splits and forms beta-amyloid. Chromosome 21 is also the chromosome involved in Down’s syndrome. As people with Down’s grow older, they develop tangles and plaques in their brains similar to those found in brains with Alzheimer’s.
  • The chemical messengers: One nerve cell communicates with another by releasing chemicals called neurotransmitters. These chemicals cross the synapse between the cells and bind to receptor molecules in the membrane of the second cell. Other substances in the cell relay the message. Since the 1970s, research has shown the level of one neurotransmitter called acetylcholine is dramatically lower than normal in people with Alzheimer’s. Much research into treating the disease concerns boosting the level of this chemical. Other neurotransmitters have also been shown to be lower in some Alzheimer’s patients but none to the same degree. Abnormalities in the receptors and other chemical messengers on the other side of the synapse also interest researchers.
  • The metabolism of glucose: Nerve cells depend on glucose, a sugar molecule, for energy. When the metabolism of glucose is disturbed, the cells may not be able to manufacture neurotransmitters such as acetylcholine or they may react abnormally to such chemical messengers. Eventually they die. Researchers are trying to find out whether the decline in glucose metabolism they see in patients with Alzheimer’s is because of the disease or causes the disease.
  • The amount of calcium: Nerve cells need calcium to transmit signals. Too much calcium, however, can kill a cell; so the amount is carefully regulated by various mechanisms. A breakdown in any one of the mechanisms could cause the degeneration of nerve cells seen in Alzheimer’s.
  • The environment: The most studied environmental factors that may play a role in causing Alzheimer’s are aluminum, zinc, food-borne poisons and viruses.

Risk factors

Studying risk factors not only helps warn people of their chances of developing a disease, it can provide clues to the disease’s causes. Risk factors for Alzheimer’s are divided into ones that are well established and others that are still considered only probable. None of the risk factors predict development of the disease. They simply suggest an increased risk.

Well-established factors

  • Increasing age: Simply put, the older you are, the greater the risk.
  • Family history: A strong case for a genetic cause is made on three fronts. A Finnish study on identical twins showed if one twin developed Alzheimer’s, the other had a 40 percent to 50 percent chance of developing it, too. Yet another study called MIRAGE that tracked the lifetime risk of nearly 13,000 relatives of people with Alzheimer’s found remarkable results. People with two parents with the disease were five times more likely to get it than people with two unaffected parents. A separate study showed there were specific genes in families with a history of Alzheimer’s as well as in people with Down’s syndrome.
  • Being female: The MIRAGE study also showed women have a higher risk of Alzheimer’s disease at every age.
  • Environmental factors: Because the identical twin of an Alzheimer’s patient does not have a 100 percent chance of developing the disease, environmental factors probably influence any genetic predisposition. In another study, elderly Japanese men living in Hawaii were compared with a similar demographic group remaining in Japan. The findings suggest factors associated with migrating to Hawaii increased the risk of Alzheimer’s to that of white Americans and Europeans. Also, various studies have linked specific environmental factors, such as zinc and food-borne poisons, with damage to nerve cells.

Probable factors

  • The increased presence of the ApoE4 gene can be detected by laboratory tests.
  • Infrequent use of NSAIDs appears associated with increased risk. Studies show people with severe arthritis or leprosy who are treated with large doses of these medications exhibit a lower incidence of Alzheimer’s than the general population. A survey of more than 1,800 people by the National Institute On Aging further indicated the longer people took NSAIDs, the lower their risk. Other studies looked at people with Alzheimer’s, some who took NSAIDs regularly and some who did not. Those who took NSAIDs exhibited a slower mental decline. Because inflammation plays a role in developing tangles and plaques, NSAIDs may protect against the damage.
  • Post-menopausal women who do not use hormone replacement therapy may be at higher risk. Studies show women who take estrogen as hormone replacement therapy are less likely to develop Alzheimer’s. Those who have Alzheimer’s and take the hormone suffer less severe symptoms and show a slower mental deterioration. In one study on 12 female Alzheimer’s patients, the women improved in cognitive test scores after just one week on the hormone.
  • Deficiency of antioxidant nutrients such as vitamins A, C and E, and the mineral selenium may allow highly reactive oxygen molecules called free radicals to damage brain cells.
  • Head injuries that result in loss of consciousness have been associated with increased risk of Alzheimer’s.
  • Heart disease, stroke and high blood pressure all damage blood vessels that carry oxygen and nutrients to the brain and may contribute to the development of Alzheimer’s.
  • The less formal a person’s education, the more likely he or she is to develop Alzheimer’s.

Not one cause but many?

In the end, Alzheimer’s may turn out to be a medical whodunit with many culprits all interacting and influencing each other, but not one of them causing the disease on its own. Whatever the cause or combination of causes, researchers have a way to go before solving the mystery.

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