Introduction:
Alzheimer's disease is a progressive neurological disorder primarily affecting memory and cognitive function. It is the most common dementia cause, which impairs one's capacity for thought, reasoning, and behavior. Though the precise origin is still unknown, it is believed to be connected to abnormal protein deposits that accumulate in the brain and cause the death of brain cells. As the symptoms increase, they affect functionality and day-to-day living. Alzheimer's disease now has no known cure; however, some interventions and treatments can help manage symptoms and improve the quality of life for people who are affected.
While someone does not need to have a family history of developing Alzheimer's, studies indicate that individuals with a parent or sibling with Alzheimer's face a higher risk than those without a first-degree relative with the disease. The risk increases further if there is more than one first-degree relative with Alzheimer's. A mix of hereditary and environmental variables may increase the risk of Alzheimer's disease and other dementias when they run in families.
What Are Alzheimers Genes?
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Several genes increase the risk of Alzheimer's disease. Every single cell in the body has its functions regulated by genes. Certain genes control basic characteristics such as hair and eye color, while other genes increase a person's risk of developing several disorders, including Alzheimer's.
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The Apolipoprotein E (APOE) gene is the main cause of late-onset Alzheimer's dementia, which usually appears around age 65. There are three typical kinds of APOE: The least common APOE, e2, lowers the risk of Alzheimer's; the most frequent APOE, e4, increases the risk and is linked to a more severe form of the illness; and the most common APOE, e3, does not seem to affect the risk of Alzheimer's.
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The APOE gene is inherited from both parents, with one copy coming from each. Alzheimer's disease risk is doubled or tripled if at least one APOE e4 gene is present. A person may inherit one APOE e4 gene from each parent. An additional eight to twelve times higher chance of developing Alzheimer's disease results from having two genes.
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However, not all individuals with one or more APOE e4 alleles get Alzheimer's disease. In addition, the disease strikes a large number of non-APOE e4 gene carriers. This implies that rather than being a cause, the APOE e4 gene raises risk. Alzheimer's disease is probably influenced by a person's lifestyle, race, ethnicity, and environment in addition to their genes.
Late Onset Genes:
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ABCA7: There seems to be a connection between this gene and an increased risk of Alzheimer's. Scientists speculate that it might be related to the gene's function in regulating the body's utilization of cholesterol.
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CLU: This gene aids in the brain's removal of the amyloid-beta protein. Studies indicate that the development of Alzheimer's disease may be attributed to an imbalance in the production and clearance of amyloid-beta (protein).
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CR1: Insufficient amounts of the protein that this gene produces may result in inflammation or long-term swelling and irritation in the brain. Another potential risk factor for Alzheimer's disease is inflammation.
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PICALM: This gene is associated with how brain nerve cells, called neurons, speak to one another. Their communication style is crucial for them to function effectively and create memories.
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PLD3: Research is ongoing regarding PLD3's function in the brain. However, there has now been evidence connecting it to a markedly elevated risk of Alzheimer's disease.
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TREM2: This gene influences the way the brain reacts to inflammation, which is defined as swelling and discomfort. An elevated risk of Alzheimer's disease is linked to rare alterations in this gene.
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SORL1: On chromosome 11, there are variants of SORL1 that seem to be connected to Alzheimer's. More research is being done to better understand Alzheimer's disease. New approaches to the disease's prevention and treatment may result from a deeper understanding of its mechanisms.
Similar to APOE, these genes are not causes but rather risk factors. Put another way, there may be a higher chance of Alzheimer's if they have one of these altered genes. However, not every individual with a mutated gene will get Alzheimer's disease.
Young Onset Alzheimer's:
The young-onset form of Alzheimer's affects a relatively tiny percentage of persons. This kind of symptom commonly manifests between the ages of 30 and 60. There is a clear genetic component to this kind of Alzheimer's.
Researchers have identified three genes that are altered to produce Alzheimer's disease with an early onset. Before the age of 65, Alzheimer's symptoms are likely to appear in anyone who inherits one of these gene mutations from either parent. The genes are:
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Amyloid precursor protein (APP).
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Presenilin 1 (PSEN1).
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Presenilin 2 (PSEN2).
Mutations in these genes result in the overproduction of the amyloid-beta peptide fragment of a protein. Amyloid plaques are aggregates that can accumulate in the brain due to this poisonous peptide. A defining feature of Alzheimer's disease is these plaques. The accumulation of amyloid plaques and toxic amyloid-beta peptides can cause nerve cell death and the symptoms of Alzheimer's disease.
Tau proteins malfunction in the brain as a result of amyloid plaque accumulation. Instead, they bind together to form tau tangles. The way Alzheimer's disease damages the brain is connected to these tangles.
Nonetheless, some individuals with early-onset Alzheimer's disease do not exhibit alterations in these three genes. That implies that further gene alterations or unidentified factors may be connected to some early-onset forms of Alzheimer's disease.
What Is the Role of Genetic Testing in Alzheimers?
Genetic testing for late-onset Alzheimer's is not commonly recommended by experts. While it may be helpful in some cases of early-onset Alzheimer's, it is not routinely done for APOE genes as the results cannot definitively predict Alzheimer's. Diagnosis is usually possible without genetic testing. However, for anti-amyloid therapies, APOE genotype testing is crucial to assess the risk of side effects. Discuss with the healthcare provider whether APOE testing is appropriate for the patients. Testing for gene changes linked to early-onset Alzheimer's may be beneficial for those with symptoms or family history, impacting medicine trials and aiding family planning. Yet, results could have consequences, affecting employment opportunities and insurance eligibility.
Conclusion:
Scientists suspect that there are still undiscovered genes influencing Alzheimer's disease risk, crucial for advancing treatment and prevention. Ongoing research, such as the Dominantly Inherited Alzheimer Network (DIAN) and the Alzheimer's Disease Genetics Study, explores genes linked to the condition, including protective variants like APOE Christchurch. Participation in studies, like those organized by the National Institute on Aging, provides valuable insights into Alzheimer's genetics.
