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.
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.
