Risk Factors for Alzheimer’s Disease

This article summarizes the changes in the brain that lead to the development of a particular type of dementia, Alzheimer’s disease (AD), and describes some risk factors associated with its development.

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What is Alzheimer’s disease?

Dementia is a common term for some brain dysfunction, such as language, memory, and problem-solving abilities. There are various types of dementia, including Lewy body dementias, Korsakoff syndrome, and Huntington’s disease, but Alzheimer’s disease (AD) is the most common form, accounting for 60% to 80% of all dementia cases. I will.

AD is a degenerative brain disorder that causes symptoms of dementia that worsen over time. Early symptoms include amnesia, difficulty completing familiar tasks, or upset mood, and later symptoms include loss of ability to speak, difficulty moving, or lack of awareness of the surroundings. It will be.

What Causes Alzheimer’s Disease?

Alzheimer’s disease is caused by complex changes in nerve cells in the brain that damage neurons and eventually lead to death.

Studies show that deposits of protein beta-amyloid (called amyloid plaques) and twisted fibers of protein tau (neurofibrillary tangles), which develop with age in most brains, are more common in the brains of AD patients. Is shown. They also begin in the peroral cortex and appear in a unique pattern before spreading to the hippocampus and primary neocortex.

Plaques are thought to destroy cells by triggering an immune response in the surrounding area during the formation of tangles within the cell, disrupting the process of recycling to produce new proteins, and ultimately killing the cell. I am.

Risk Factors for Alzheimer’s Disease

age

The most important risk factor for Alzheimer’s disease is aging, and the age-specific prevalence of the disease doubles every five years after age 65. The prevalence of AD rises to 1% between the ages of 65 and 69 and to about 30% in the elderly. 90 years or older. Some age-related processes may be involved in the etiology of the disease.

Oxidative stress: Free radicals are oxygen-containing molecules that are the usual by-products of energy production by cells. At high concentrations, it can damage cell membranes and proteins, damaging tissues. Antioxidants are molecules that neutralize free radicals, and when the balance between free radicals and antioxidants is lost, oxidative stress occurs. Age-related AD is thought to be due to the accumulation of oxidative damage.

Beta amyloid: Evidence that is believed to be a major driver of AD shows that the brain’s ability to remove beta-amyloid slows with age. One study shows that it takes about four hours for people in their thirties to get rid of half of the beta-amyloid in the brain. By the age of 80, this increases to 10 hours.

Lifelong experience: The strong correlation between AD and age may be due in part to the cumulative effects of complex interactions between lifelong risk and protective factors.

Although AD and age are strongly correlated, age is not a necessary prerequisite for the development of AD. A small number of patients develop early-onset Alzheimer’s disease in their 40s and 50s.

Beta amyloid protein, which destroys nerve cells, functions in the brain with Alzheimer’s disease. Image Credit: nobeastsofierce / Shutterstock.com

Genetics

The development of certain diseases is influenced by risk and deterministic genes. Risk genes increase the likelihood of a disease, but do not guarantee it, but inheritance of a deterministic gene guarantees the development of the corresponding disease. Studies have identified both the risk of hereditary Alzheimer’s disease and deterministic genes.

Risk genes: Several genes are involved in AD risk, with the APOE-e4 gene having the greatest impact on risk. APOE-e4 promotes beta-amyloid accumulation and creates unique plaques found in the brains of AD patients, which are present in 40-65% of AD patients. APOE-e4 seems to have a dose-response effect. Those who inherit it from both parents are at increased risk of developing AD. In addition, inheriting APOE-e4 may increase the likelihood of early onset symptoms.

Deterministic genes: Early-onset Alzheimer’s disease is strongly associated with mutations in three genes. Amyloid precursor protein, presenilin 1 and presenilin 2. Individuals who inherit one of these mutations from either parent develop the disease, but such individuals make up less than 5% of all people with AD. All three mutations cause excess beta-amyloid.

Cardiovascular disease (CVD)

There is increasing evidence that there may be a causal link between CVD and cardiovascular risk factors and Alzheimer’s disease. The brain is highly angiogenic and uses one-fifth of the body’s oxygen supply, making it particularly vulnerable to the hypoperfusion of the brain, a condition that occurs when the blood supply to the brain is inadequate. is.

Hypoperfusion of the brain is hypothesized to contribute to the development of amyloid plaques and tau through conditions of oxidative stress. In addition, hypoperfusion of the brain also causes destruction of the blood-brain barrier, reducing plaque and tangle clearance.

Several risk factors associated with CVD, such as smoking, obesity, and diabetes, are also risk factors for AD, but middle-aged hypertension, independent of other cardiovascular risk factors, puts the risk of developing AD at an older age. I will raise it. Interestingly, hypertension in later years does not correlate with AD. Although the causal mechanism between hypertension and AD has not been proven, one hypothesis is that long-term hypertension is associated with hypoperfusion of the brain.

Down syndrome

By the age of 40, the brains of most people with Down’s syndrome (DS) show the characteristic pattern of plaque and tangles found in Alzheimer’s disease. However, although the prevalence of AD is high in DS patients, AD does not occur in all cases. AD is found in about 30% of people with a DS in their 50s and rises to 50% of people with a DS in their 60s. Understanding why AD affects only some people, despite the presence of such changes in the brain, is a very interesting area for researchers.

Head injury

Some studies have shown that moderate or severe head injuries can increase the risk of developing Alzheimer’s disease years later. One important study found that persistent moderate head injuries increased the risk of AD by a factor of 2.3 and severe head injuries were at a 4.5 times risk.

Prospective studies show that traumatic brain injury is associated with early onset of AD. Similar to CVD, the mechanism by which this occurs is thought to be associated with hypoperfusion of the brain leading to a series of causative events that ultimately lead to the characteristic protein-related brain changes observed in AD. I am.

References

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Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., Gargiulo, G., Testa, G., Cacciatore, F., Bonaduce, D .. , & Abete, P. (2018). Oxidative stress, aging, and illness. Clinical intervention in aging, 13, 757–772. https://doi.org/10.2147/CIA.S158513

Qiu, C., Kivipelto, M. , And von Strauss, E. (2009). Epidemiology of Alzheimer’s disease: Outbreaks, determinants, and strategies for intervention. Dialogue in clinical neuroscience, 11(2), 111-128. https://doi.org/10.31887/DCNS.2009.11.2/cqiu

Safieh, M., Korczyn, AD & Michaelson, DM ApoE4: New therapeutic targets for Alzheimer’s disease. BMC Med 17, 64 (2019). https://doi.org/10.1186/s12916-019-1299-4

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References