In order to understand the genetics of Alzheimer's disease (AD), it is first necessary to understand the basics of genetics. Most cells of the body have 46 chromosomes, grouped into 23 pairs. One member of each chromosome pair is transferred from parent to child during fertilization. These chromosomes are composed of deoxyribonucleic acid (DNA), which is the genetic material. Segments or sequences of DNA consist of genes, which encode many of the characteristics of each individual, including hair and eye color. Often, the variation between individuals in these traits is due to variation in the sequence of the DNA of these genes.
Many studies have been carried out to identify the factors associated with an increased risk for developing AD. Initial studies focused on those families in which members developed AD at an early age, typically under the age of 60 years. While these early-onset families comprise less than 5% of all cases of AD, they have provided important information about the genetics of AD. Changes in the DNA sequence (termed mutations) in three different genes have been found to cause AD in some of these families. These genes are called amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2).
The vast majority of cases of AD have an onset after the age of 60 years. These later-onset cases of AD are less likely to have a mutation in the sequence of the APP, PS1, or PS2 genes. Rather, individuals who develop AD later in life are more likely to have developed the disease due to a combination of environmental and genetic risk factors. A gene, termed apolipoprotein E (ApoE), has been found to be an important risk factor for later onset AD.
The APP, PS1, and PS2 genes are all considered to be causative genes that, when their DNA segments are altered, can cause AD. An important distinction must be made with ApoE. Variation in the DNA sequence of ApoE can increase or decrease the risk that an individual will develop AD; however, it is thought that variation in ApoE alone does not determine whether an individual will develop AD. Therefore, ApoE is often called a susceptibility factor.
It is clear that other genes must also play an important role in affected AD susceptibility. Studies using samples collected and distributed by the National Cell Repository for Alzheimer's Disease will help scientists identify the other important genes contributing to AD susceptibility.
For more information about genetics, please see the Alzheimer's Disease Genetics Fact Sheet from the Alzheimer’s Disease Education & Referral Center (ADEAR) website.