When I was in college, my grandmother was diagnosed with Alzheimer’s disease. Over the course of 5-10 years, she continued to decline, at first mixing up simple things like the difference between the microwave and the oven, and later not recognizing any of her grandchildren. The one constant in her condition was she never forgot my grandfather, who always stayed by her side. Alzheimer’s disease is a debilitating disease that typically affects older individuals but can also affect younger individuals in certain types of Alzheimer’s disease. 

Alzheimer’s disease typically starts with dementia or a subtle failure of memory. Over time dementia can become more severe and include confusion, poor judgment, language disturbance, visual complaints, agitation, withdrawal, and hallucinations. Towards the end, Alzheimer’s disease can also manifest as seizures, muscle problems, and mutism. The disease typically lasts 8 – 10 years with slow progression. Diagnosis of Alzheimer’s disease includes a neurological assessment and imaging of the brain to look for plaques that develop during the progression of the disease that hinders brain function. 

There are multiple causes of Alzheimer’s disease (AD), including late-onset and early-onset familial. Approximately 25% of all AD is familial, which can only be distinguished from nonfamilial by family history. Late-onset familial AD (age greater than 60-65 years) is a complex disease that may involve multiple genes. One of the more commonly known genes involved in late-onset familial AD is the APOE gene. The APOE gene currently does not appear to be very accurate in predicting if a person will develop AD. There are three different changes in the APOE gene, called allele variants, that are tested: e2, e3, and e4. We have two copies of every gene, one from our mother and one from our father. If the two copies of the APOE gene are e4/e4 or e3/e4 then there is an increased risk for early or late-onset AD, but that doesn’t necessarily mean the individual will develop AD. The e2 allele appears to have a protective effect when found in individuals. More than 20 additional genes have been identified that slightly increase the risk of AD when mutated. 

Early-onset familial AD occurs in individuals before age 65 years. There are three genes that are known to be involved with early-onset AD. PSEN1 accounts for 20-70% of early-onset AD. When a mutation is found, individuals typically develop AD in their 40s or early 50s, with a rapid progression of the disease in 6-7 years. Mutations in the PSEN2 gene account for 5% of early-onset AD but has been found in some asymptomatic individuals. The last gene associated with early-onset AD is the APP gene and accounts for 10-15% of cases of early-onset AD. These genes when mutated are passed down in generations in an autosomal dominant pattern, meaning each family member has a 50% risk to also inherit the gene mutation. 

The most important indicators of a genetic form of AD is the age the disease started in an individual and their family history. Individuals diagnosed with AD can ask their family members if anyone has experienced dementia, confusion, or had a diagnosis of AD. There are genetic testing options available if an individual has a personal diagnosis or a family history of AD and wants to know their risks. 

If you are interested in learning more about AD, have a personal and/or family history of AD, and would like to pursue genetic testing, please contact AT-GC to schedule an appointment with a genetic counselor. 

By: Kendra Frome, MS, CGC
Licensed, Certified Genetic Counselor



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