The causes of Alzheimer’s disease are not fully understood. However, researchers believe that it is caused by a combination of genetic, lifestyle, and environmental factors that affect the brain over time.
In fewer than 5 percent of cases, Alzheimer’s disease is caused by a specific genetic change (mutation) that is directly linked with the early-onset form of the disease.
Alzheimer’s disease causes the brain cells to die, leading to significant brain shrinkage (atrophy). Scientists have found two major brain changes that are strongly implicated in the development of Alzheimer’s disease. One of these is the formation of abnormal deposits of protein fragments called beta-amyloids. Another brain change found in people with Alzheimer’s disease is tangles, which are intertwined threads of tau protein within the nerve fibers. These brain changes affect the structure and function of healthy nerve cells, gradually destroying them.
Although there is no known cause, there are several risk factors associated with the development of Alzheimer’s disease. Here are some of them:
Age is one of the most significant known risk factors for the development of Alzheimer’s disease. The likelihood of developing the condition doubles every five years after the age of 65. After the age of 85, the risk of developing the disease reaches nearly 50 percent. However, it is not just older people who are at risk of developing Alzheimer’s disease. People with rare genetic changes linked to early-onset Alzheimer’s begin to experience symptoms as early as their 30s and around one in 20 people with the early-onset condition are under 65.
Scientists are investigating how age-related changes in the brain may harm neurons and contribute to Alzheimer’s disease. These age-related changes include brain inflammation, shrinking of certain parts of the brain (atrophy), production of lethal unstable molecules called free radicals, and mitochondrial dysfunction causing the breakdown of energy production within a cell.
Family history and genetics
The risk of developing Alzheimer’s disease appears to be higher if a close relative (parent or sibling) has the disease. There are two categories of genes that influence whether an individual develops the disease — risk genes and deterministic genes.
Risk genes increase the likelihood of developing a disease but do not necessarily mean that the person having a certain variant of a risk gene will certainly develop the disease. Researchers have found several risk genes. APO-e4 (apolipoprotein e4), one of the three forms of the APOE gene (APO-e2, APO-e3, and APO-e4), was the first risk gene identified and was found to have the strongest effect on increasing the risk of developing the disease.
Deterministic genes directly cause a disease. Mutations in these genes cause early-onset Alzheimer’s disease that occurs when a person is between their 30s and their mid-60s. This type of Alzheimer’s disease represents fewer than 10 percent of all people with the disease.
Mutations in deterministic genes that cause the disease have been found to be located on one of three chromosomes: 21, 14 and 1. Mutations on chromosome 21 cause the formation of the abnormal amyloid precursor protein (APP). A mutation in chromosome 14 causes the formation of an abnormal form of a protein called presenilin 1, and a mutation on chromosome 1 leads to the abnormal presenilin 2 protein. All these genes affect the processing or production of beta-amyloid and brain cell death.
Many people with Down syndrome are at a higher risk of developing Alzheimer’s disease. This is because people with Down syndrome have an extra copy of chromosome 21 and therefore a higher risk of carrying the Alzheimer’s disease-causing mutation, increasing the risk of amyloid plaques to build up in the brain over time. Signs and symptoms of Alzheimer’s disease tend to appear 10 to 20 years earlier in people with Down syndrome compared to the general population.
The risk of developing Alzheimer’s disease seems to be higher in females than males. The reason for this is not fully understood, but it may in part be because women tend to live longer.
Mild cognitive impairment
People with mild cognitive impairment who have a decline in cognitive ability have an increased risk of developing dementia in later life. Strategies to develop a healthy lifestyle and prevent memory loss at this stage may help delay or prevent the progression of the condition to dementia.
Past head trauma
People who have had a severe head injury seem to have a greater risk of developing Alzheimer’s disease in later life.
Lifestyle and heart health
No specific lifestyle factor has been found to definitively reduce the risk of Alzheimer’s disease. However, some evidence suggests that the same factors that increase the risk of heart disease may also increase the risk of developing Alzheimer’s. Examples include lack of exercise, obesity, smoking or exposure to secondhand smoke, high blood pressure, high blood cholesterol, poorly controlled type 2 diabetes, and a diet lacking in fruits and vegetables.
Lifelong learning and social engagement
Studies have found that lifelong involvement in mentally and socially stimulating activities may reduce the risk of developing Alzheimer’s disease. Low education levels — less than a high school education — also appear to be a risk factor for Alzheimer’s disease.
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