Alzheimer’s disease is a neurodegenerative disorder that mainly affects people over the age of 65 years. It has been estimated that this disease currently affects over 47 million people worldwide and the number is expected to triple by the year 2050.

The symptoms of this disease can be very distressful and involve cognitive decline, memory loss, and impaired ability to communicate with others. Although Alzheimer’s disease is associated with several risk factors, including age, family history, and lifestyle habits, one of the most significant factors is genetics.

What is Alzheimer’s Disease?

Alzheimer’s is a progressive and fatal brain disorder that erodes the memory and cognitive abilities of an individual. This disease affects the hippocampus, which is the part of the brain responsible for forming new memories.

As this disease progresses, it damages other parts of the brain such as the amygdala, which is responsible for regulating emotions, and the frontal cortex, which controls language, planning, and reasoning. Although the cause of Alzheimer’s is not yet definitively known, it is largely understood to be the buildup of abnormal proteins in the brain.

These proteins, called beta-amyloid and tau, accumulate in the brain and interfere with normal brain function, causing the hallmark symptoms of Alzheimer’s disease.

The Genetic Basis of Alzheimer’s Disease

A significant body of research indicates that the risk of developing Alzheimer’s disease is largely determined by genetics. It has been found that there are several genes that are associated with the development of this disease:.

1. APOE gene

The APOE gene, located on chromosome 19, is the most significant genetic risk factor associated with Alzheimer’s disease. There are three different alleles of this gene, with the ε4 allele being the most well-known.

Individuals who carry the ε4 allele of the APOE gene are three to five times more likely to develop Alzheimer’s disease than individuals who do not carry this allele. The exact mechanism by which this allele impacts the pathology of the disease is not fully understood, but it is believed that it increases the production of beta-amyloid proteins in the brain.

2. PSEN1 gene

The PSEN1 gene is located on chromosome 14 and is responsible for encoding the presenilin-1 protein, which is involved in the breakdown of amyloid precursor protein (APP) in the brain.

Mutations in the PSEN1 gene account for approximately 50% of all early-onset familial Alzheimer’s disease cases. These mutations increase the production of beta-amyloid proteins, leading to their buildup in the brain and the development of Alzheimer’s disease.

3. PSEN2 gene

The PSEN2 gene, located on chromosome 1, is responsible for encoding the presenilin-2 protein. Mutations in this gene are less common than those in the PSEN1 gene, but they still account for some cases of early-onset familial Alzheimer’s disease.

4. APP gene

The APP gene is located on chromosome 21 and encodes the amyloid precursor protein. Mutations in this gene that increase the production of beta-amyloid are associated with early-onset familial Alzheimer’s disease.

The Inheritance of Alzheimer’s Disease

Alzheimer’s disease can be inherited in one of two ways, either as a familial autosomal-dominant trait or as a sporadic trait.

Familial Alzheimer’s disease is caused by mutations in one of the genes mentioned above, and it is inherited in an autosomal-dominant pattern. This means that if one parent has the disease-causing mutation, each child will have a 50% chance of inheriting the mutation and developing Alzheimer’s disease.

On the other hand, sporadic Alzheimer’s disease is not caused by a single genetic mutation but rather by the complex interaction between multiple genes and environmental factors.

This type of Alzheimer’s disease is much more common, accounting for approximately 95% of all cases of the disease.

Other Genetic Risk Factors for Alzheimer’s Disease

Besides the genes mentioned above, there are other genetic risk factors that play a role in the development of Alzheimer’s disease. These include:.

1. ABCA7 gene

ABCA7, located on chromosome 19, is a gene that plays a role in the immune system and in the removal of beta-amyloid proteins in the brain.

Some studies have shown that certain variants of the ABCA7 gene may increase the risk of developing Alzheimer’s disease.

2. CR1 gene

The CR1 gene, located on chromosome 1, is involved in the immune system’s response to inflammation. Variants of this gene have been associated with an increased risk for Alzheimer’s disease.

3. SORL1 gene

The SORL1 gene, located on chromosome 11, is responsible for the production of the sortilin-related receptor.

This protein is involved in the clearance of beta-amyloid proteins from the brain, and variants of this gene have been associated with an increased risk of developing Alzheimer’s disease.

Conclusion

In conclusion, genetics plays a significant role in the development of Alzheimer’s disease.

While the disease is largely sporadic, certain genetic mutations that increase the production of beta-amyloid proteins in the brain can lead to the early-onset familial form of the disease.

Further research is needed to better understand the complex interactions between genetics, lifestyle factors, and environmental factors that cause sporadic Alzheimer’s disease, but in the meantime, it is essential for individuals to maintain a healthy lifestyle that includes regular exercise, a balanced diet, and mental stimulation to help reduce their risk of developing this devastating disease.