The Genetics of Alzheimer’s Disease

Research shows that many factors are in play when it comes to the development and progression of Alzheimer’s disease. This is a debilitating neurodegenerative (brain) disease that destroys brain cells and causes many cognitive issues. The more that the disease is studied, the more scientists are able to recognize specific genes and their critical role in the development through its varying stages.

What is Alzheimer’s Disease?

Alzheimer’s disease is an irreversible, progressive, and destructive disease. It is marked by the development of plaques of a protein called amyloid. The protein tangles called tau within neurons (brain cells). Due to these abnormalities within the neurons, there are losses of connections of the cells in the brain, causing the death of these cells. This directly attributes to the main symptoms and signs of the disease.

Two primary types of the disease have been defined. Though, the genetics and causes of each type are exceptionally different. We will examine the genes behind each type of the disease and how it impacts the individual.

What Are Signs of Alzheimer’s Disease?

According to the Alzheimer’s Association, there are ten early signs that can be indicators of the disease.

  • Memory loss that disrupts daily life (besides normal changes in cognition that come with age)
  • Challenges with problem-solving or difficulty with numbers
  • Difficulty completing familiar tasks at home, at work, or at leisure
  • Confusion with time and place (and being unable to solve the issue later on)
  • Trouble understanding images and spatial relationships
  • New problems with words or in speaking/writing
  • Misplacing things and being unable to retrace steps
  • Decreased or poor judgment
  • Withdrawal from work, social activities, or activities that bring someone joy
  • Changes in mood or personality

Diagnosis based on these symptoms alone can sometimes be difficult. Some ways to determine if the symptoms are the disease in these cases can be done through mental status testing or by blood testing.

The Different Types of Alzheimer’s Disease

There are two primary types of the disease that are primarily characterized by the time of onset in an individual’s life.

The first is known as early-onset Alzheimer’s disease. This type of the disease occurs early in life, hence its name. The typical ages of onset range from their 30s to their mid-60s. This range represents a small portion of patients of the disease – approximately 10%.

It’s believed that in some of these cases, the disease is caused by an inherited change in one of three specific genes, resulting in early-onset familial Alzheimer’s disease, or FAD. In other cases, research has found that other genetic components can come into play besides these three particular genes. A child whose biological parent carries a mutation in their genes, or an abnormal genetic pattern, for early-onset FAD has a 50% chance of inheriting that mutation. If the mutation is inherited, there is a strong possibility that the individual will have FAD.

Most individuals impacted by Alzheimer’s disease (90%+) have the second or late-onset type of the disease. This is when symptoms are found in the late-60s and later in life. The causes of late-onset Alzheimer’s could likely include a combination of genetic, environmental, and lifestyle factors that affect a person’s risk for developing the disease.

What Genes Are Involved in Alzheimer’s Disease?

With two primary forms of the disease, different genes are at play.

  • 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.
    • A mutation on chromosome 1 leads to abnormal presenilin 2.
      • APP is the precursor molecule to beta-amyloid, otherwise known as A-beta. This is a polypeptide – containing 37 to 49 amino acid residues. Polypeptides form together to create proteins. When these proteins begin to combine, they form plaques, one of the major hallmarks of the disease in neurons.
      • The two types of Presenilin are part of a larger protein complex that is able to break down APP. With mutations causing these to be made abnormally, they are unable to break down APP. Therefore unable to break down plaques. This causes the plaques to continue to form and to kill the neurons, leading to further degradation of the neurons. And the furthering of the disease.
  • Within late-onset Alzheimer’s disease, researchers have not been able to identify a gene directly causes its onset. However, one major risk factor has been found – the presence of the apolipoprotein E (APOE) gene on chromosome 19.
    • APOE comes in several different forms. The specific type that is thought to cause the disease is APOE ε4. The more forms that an individual has, researchers believe the greater the chance the individual develops the disease.

As discussed in our blog about the Genetics of Migraines, Genome-Wide Association Studies (GWAS) have been done for Alzheimer’s Disease as well. Through these studies, by 2015, research has confirmed 33 regions of interest in the Alzheimer’s genome.

How Can I Find Out If I’m At Risk?

Blood testing can be done to determine which APOE allele an individual may have, but it is not 100% accurate. Another way to determine if you are currently having abnormal cognitive symptoms is through memory testing. At Meridien Research, we are proud to offer these free of charge.

To schedule a free memory screen, get more information on currently enrolling studies or see if you or someone you know may qualify, please contact us today at 1-888-777-8839 or check our current studies online.