Alzheimer's Disease and other Dementias
Alzheimer's and The Genetic Factor
Scientists believe that many factors influence when Alzheimer’s disease begins and how it progresses. The more they study this devastating disease, the more they realize that genes play an important role. Research conducted and funded by the National Institute on Aging (NIA) at the National Institutes of Health (NIH) and others is advancing our understanding of Alzheimer’s disease genetics.
The Genetics of Disease
Some diseases are caused by a genetic mutation, or permanent change in one or more specific genes. If a person inherits from a parent a genetic mutation that causes a certain disease, then he or she will usually get the disease. Sickle cell anemia, cystic fibrosis, and early-onset familial Alzheimer’s disease are examples of inherited genetic disorders.
In other diseases, a genetic variant may occur. A single gene can have many variants. Sometimes, this difference in a gene can cause a disease directly. More often, a variant plays a role in increasing or decreasing a person’s risk of developing a disease or condition. When a genetic variant increases disease risk but does not directly cause a disease, it is called a genetic risk factor.
Identifying genetic variants may help researchers find the most effective ways to treat or prevent diseases such as Alzheimer’s in an individual. This approach, called precision medicine, takes into account individual variability in genes, environment, and lifestyle for each person.
Alzheimer’s Disease Genetics
Alzheimer’s disease is an irreversible, progressive brain disease. It is characterized by the development of amyloid plaques and neurofibrillary, or tau, tangles; the loss of connections between nerve cells (neurons) in the brain; and the death of these nerve cells. There are two types of Alzheimer’s—early-onset and late-onset. Both types have a genetic component.
Early-Onset Alzheimer’s Disease
Early-onset Alzheimer’s disease occurs in people age 30 to 60 and represents less than 5 percent of all people with Alzheimer’s. Most cases are caused by an inherited change in one of three genes, resulting in a typle known as early-onset familial Alzheimer’s disease, or FAD. For others, the disease appears to develop without any specific, known cause.
A child whose biological mother or father carries a genetic mutation for early-onset FAD has a 50⁄50 chance of inheriting that mutation. If the mutation is in fact inherited, the child has a very strong probability of developing early-onset FAD.
Early-onset FAD is caused by any one of a number of different single-gene mutations on chromosomes 21, 14, and 1. Each of these mutations causes abnormal proteins to be formed. Mutations on chromosome 21 cause the formation of abnormal amyloid precursor protein (APP). A mutation on chromosome 14 causes abnormal presenilin 1 to be made, and a mutation on chromosome 1 leads to abnormal presenilin 2.