Alzheimer's Disease (AD) is a progressive neurological disorder that primarily affects memory, thinking, and behaviour. Among older adults, it is the most common cause of dementia, a neurodegenerative disease and the sixth leading cause of death. Factors, such as genetics, environment and lifestyle influence the development of Alzheimer’s. Among these, family history and genetic predispositions play significant roles. We spoke to our expert Dr Mahendra JV, HOD and Consultant-Department of Neurology, Ramaiah Institute of Neurosciences, Ramaiah Memorial Hospital, Bengaluru, who explained the connection between family history and the risk of AD.
According to a 2015 study, about 10% of all people above 65 years and 50% above 85 years of age suffer from AD. Alzheimer's disease is linked to increasing age and a positive family history of the disease. The risk is higher if the mother has AD compared to the father. Additionally, women are at greater risk of developing AD, which has been linked to the decline in oestrogen levels after menopause.
Family History and Alzheimer’s Disease
“Family history is a well-known risk factor for Alzheimer's disease. Individuals with a first-degree relative (parent, sibling) diagnosed with Alzheimer's are more likely to get the illness than those without such a family history,” said Dr JV.
If more than one family member is impacted, the risk is much higher. This family aggregation indicates a substantial hereditary component to the condition.
Also Read: Alzheimer's Disease: Expert Explains 7 Stages Of This Condition
Genetic Factors in Alzheimer’s Disease
The genetic basis of Alzheimer's disease can be divided into two categories: early-onset familial Alzheimer's disease (EOFAD) and Late-Onset Alzheimer's Disease (LOAD).
1. Early-Onset Familial Alzheimer's Disease (EOFAD)
EOFAD accounts for less than 5% of all Alzheimer's cases and typically manifests before the age of 65. This form of Alzheimer's is strongly linked to mutations in three specific genes:
a. Amyloid Precursor Protein (APP): Mutations in the APP gene can lead to abnormal production of amyloid-beta, a protein that aggregates to form plaques in the brains of Alzheimer's patients.
b. Presenilin 1 (PSEN1): Mutations in the PSEN1 gene are the most common cause of EOFAD. In response to these mutations, amyloid-beta production increases due to a change in the processing of amyloid precursor protein.
c. Presenilin 2 (PSEN2): Mutations in the PSEN2 gene are less common but also lead to increased amyloid-beta production.
Individuals with mutations in any of these genes have a nearly 100% chance of developing Alzheimer's disease, often at a younger age.
2. Late-Onset Alzheimer’s Disease (LOAD)
LOAD is the most common form of Alzheimer's and typically occurs after the age of 65. While the specific reason is not fully known, some genetic risk factors have been identified:
a. Apolipoprotein E (APOE): The APOE gene is the most important genetic risk factor for LOAD. This gene has three common alleles: ε2, ε3, and ε4. The ε4 allele is linked to a higher risk of developing Alzheimer's, with the risk being greater in individuals who have two ε4 alleles compared to those with one. Conversely, the ε2 allele seems to provide a protective effect.
b. Other Genetic Variants: Advances in Genome-Wide Association Studies (GWAS) have identified several other genetic variants associated with an increased risk of LOAD. These include variants in genes involved in immune response, lipid metabolism, and synaptic function, such as TREM2, SORL1, and CLU.
Also Read: 10 Early Signs And Symptoms Of Alzheimer's And Dementia
Role of Genetic Testing
“Genetic testing can help determine an individual's risk of acquiring Alzheimer's disease, especially in families with a history of EOFAD. Testing for the APOE ε4 allele in individuals with a family history of LOAD can provide insight into risk, but it is not conclusive,” said Dr JV.
While genetic testing can be useful, it is critical to address the psychological and societal consequences. Knowing one's hereditary risk might cause worry and influence personal decisions. As a result, genetic counselling is suggested to assist individuals in understanding the potential outcomes and consequences of testing.
Environmental and Lifestyle Factors
“Although genetic factors play an important role in Alzheimer's disease, they cannot account for all instances. Environmental and behavioural factors also increase the risk. These factors include age, cardiovascular health, such as hypertension, diabetes, high cholesterol, education and cognitive engagement, and diet and exercise,” highlighted Dr JV.
Bottomline
Dr JV concluded, “The connection between family history, genetics, and Alzheimer's disease is complicated. Understanding the disease's genetic features, especially EOFAD-related mutations and the APOE ε4 allele, offers crucial insights into an individual's risk. However, environmental and lifestyle variables play important roles and provide opportunities for risk reduction. Ongoing research uncovers novel genetic variations and pathways implicated in Alzheimer's disease, offering improved risk assessment, early identification, and perhaps tailored therapeutics in the future.”
[Disclaimer: This article contains information provided by an expert and is for informational purposes only. Hence, we advise you to consult your expert if you are dealing with any health issues to get the necessary treatment.]