What causes Alzheimer’s disease?
In recent years, scientists have made tremendous progress in better understanding Alzheimer’s and the momentum continues to grow. Still, scientists don’t yet fully understand what causes Alzheimer’s disease in most people. The causes probably include a combination of age-related changes in the brain, along with genetic, environmental, and lifestyle factors. The importance of any one of these factors in increasing or decreasing the risk of developing Alzheimer’s may differ from person to person.
The basics of Alzheimer’s disease
Scientists are conducting studies to learn more about plaques, tangles, and other biological features of Alzheimer’s. Advances in brain imaging techniques enable researchers to see the development and spread of abnormal amyloid and tau proteins in the living brain, as well as changes in brain structure and function. Scientists are also exploring the very earliest steps in the disease process by studying changes in the brain and body fluids that can be detected years before Alzheimer’s symptoms appear. Findings from these studies will help improve our understanding of the causes of Alzheimer’s and make diagnosis easier.
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One of the great mysteries of Alzheimer’s is why it largely affects older adults. Research on normal brain aging is exploring this question. For example, scientists are learning how age-related changes in the brain may harm neurons and affect other types of brain cells to contribute to Alzheimer’s damage. These age-related changes include atrophy (shrinking) of certain parts of the brain, inflammation, blood vessel damage, production of unstable molecules called free radicals, and mitochondrial dysfunction (a breakdown of energy production within a cell).
Alzheimer’s disease genetics
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In most cases, Alzheimer’s does not have a single genetic cause. Instead, it is likely influenced by multiple genes in combination with lifestyle and environmental factors. Changes in genes, called genetic variations, may increase or decrease a person’s risk of developing the disease.
Scientists currently know of more than 80 genetic regions associated with Alzheimer’s. Of the genetic variants associated with Alzheimer’s so far, only three are known to cause the disease. Although it happens rarely, when someone inherits an altered version of one of these genes — APP, PSEN1, or PSEN2 — they will likely develop Alzheimer’s before age 65 and sometimes much earlier.
People with Down syndrome also have a higher risk of developing Alzheimer’s earlier in life. Down syndrome results from having an extra chromosome 21, which carries the APP gene that produces the amyloid precursor protein. Too much of this protein leads to build-up of beta-amyloid plaques in the brain. Estimates suggest that 50% or more of people living with Down syndrome will develop Alzheimer’s with symptoms appearing in their 50s and 60s.
Another genetic variation, in the APOE gene, which has several forms, is known to influence the risk of Alzheimer’s. Specifically, APOE ε4 increases a person’s risk of developing Alzheimer’s and is also associated with developing Alzheimer’s earlier in life for certain populations. APOE ε2 may provide some protection against Alzheimer’s.
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Changes in different genes, along with other biomedical, lifestyle, and environmental factors, play a role in potentially developing Alzheimer’s. Still, it is never known for certain if any individual will or will not develop the disease.
For more about Alzheimer’s genetics research, see NIA’s Alzheimer’s Disease Genetics Fact Sheet.
Health, environmental, and lifestyle factors
Research suggests that a host of factors beyond genetics may play a role in the development and course of Alzheimer’s. There is a great deal of interest, for example, in the relationship between cognitive decline and vascular conditions, such as heart disease, stroke, and high blood pressure, as well as metabolic diseases, such as diabetes and obesity. Ongoing research will help us understand whether and how reducing risk factors for these conditions may also reduce the risk of Alzheimer’s.
A nutritious diet, physical activity, social engagement, and mentally stimulating pursuits have all been associated with helping people stay healthy as they age. These factors might also help reduce the risk of cognitive decline and Alzheimer’s. Researchers are testing some of these possibilities in clinical trials.
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