What is Alzheimer’s Disease (AD)?
Dementia is a category of diseases that affect cognitive functions such as memory and language. Alzheimer’s disease is the most common type of dementia accounting for about 60-80% of cases.
It is a degenerative brain disease that causes memory loss, difficulty planning and performing daily activities. It is also a progressive disease where the symptoms worsen over time. For example, forgetting appointments, constantly misplacing belongings and forgetting how to perform usual daily tasks. These symptoms can progress into more drastic behavioral changes such as impairments to speaking and walking. Alzheimer’s disease is most common in people over the age of 65 but can affect younger age groups as well. Early onset Alzheimer's disease (EOAD) can occur in 30-, 40-, and 50-year-olds. This can happen from familial genes passed on which makes Alzheimer testing important for those with a family history of the disease.
An estimated one in twenty people with AD have the early-onset form (EOAD). Pathogenic variants in 3 main genes account for the large majority of inherited early-onset AD: APP (amyloid precursor protein), presenilin 1 (PSEN1) and presenilin 2 (PSEN2).
Much more commonly, the clinical symptoms and signs of AD become apparent later in life and the condition is called late-onset Alzheimer’s disease (LOAD or “sporadic AD”). In the case of LOAD, the genetic factor that has been predominantly associated with the condition is the ε4 version of the apolipoprotein gene referred as APOE ε4. This variant of the gene is known to increase the risk of LOAD by a factor of 2 or 3. People who have two copies of ε4 have up to a 12-fold risk. APOE testing can not fully predict who will or won’t develop the condition.
An additional number of genes have been identified that increase the risk of developing LOAD. However, it is important to know that a genetic factor alone is not sufficient to explain LOAD. Instead, it can be influenced by multiple genes in combination with lifestyle and environmental factors.
Who should be taking this test?
People with a family history of AD can be tested to determine if they are at risk of developing the disease. Importantly, people who develop Alzheimer’s do not always have a history of the disease in their families. Still, those who have a parent or sibling diagnosed with the condition have a higher risk of developing Alzheimer’s than those without that association.
Patients with EOAD can benefit from the test as it could be used to clarify the reason for the cognitive decline. Family members of a person that has tested positive for a pathogenic variant in APP, PSN1 and PSN2 may also want to be informed of their genetic status, since they are related to an autosomal dominant mode of transmission. In this case one copy of the pathogenic variant can cause EOAD, a child who has a parent with the pathogenic variant will have a 50% chance of inheriting the abnormal gene, and thus the disease.
Those individuals showing symptoms of Alzheimer's disease such as memory impairment, difficulty concentrating and planning could be tested to determine if there is a genetic factor influencing the disease progression.
Why should they take it?
(What can they do if they get positive results).
Although as of now there is no cure for AD, there are several treatments that may change disease progression, slowing cognitive and functional decline, especially when signs of the disease are detected at early stages. Being aware of genetic risks would make people more conscious of their mental health, seeking proper attention on time in the case they start presenting any kind of cognitive decline.
Also, as medical research continues, more clinical trials will be offered to patients with distinct genetic makeup, aiming to find effective early treatment for Alzheimer’s disease.