Alzheimer's and Down Syndrome: The Curious Link
Down syndrome occurs when a person has a full or partial copy of chromosome 21. This is significant to Alzheimer’s risk because chromosome 21 carries the APP gene, which produces amyloid precursor protein (APP).
Scientists aren’t sure what the function of APP is, but they have learned that day-to-day brain activity involves continuous “processing” of APP into shorter pieces. One of the brain’s APP processing pathways produces beta-amyloid, meaning that an extra copy of the APP gene may increase the production of beta-amyloid. Researchers have also located several other genes on chromosome 21 that are involved in aging and are believed to contribute to the increased risk of Alzheimer’s in people living with Down syndrome.
Too much APP leads to the buildup of protein clumps called beta-amyloid plaques. By age 40, almost all people with Down syndrome have these plaques along with tau tangles in their brain, both of which are markers associated with Alzheimer’s. Fortunately, not all people with plaques and tangles develop symptoms of Alzheimer’s. Although all people living with Down syndrome are at risk of developing Alzheimer’s, with risk increasing each decade of life, at no point is the probability of developing Alzheimer’s 100%. About 30% of people living with Down syndrome develop Alzheimer’s by their 50s, and about 50% develop Alzheimer’s by their 60s. Researchers aren’t sure why some people with Down syndrome develop dementia and others don’t. It is also worth noting that the type of Alzheimer’s experienced by people living with Down syndrome is not passed down from parent to child.
Alzheimer’s is a clinical diagnosis, which means that doctors rely on information provided by the patient, caregiver, and other reliable sources, and then provide a diagnosis based on their judgment. There is no blood test, x-ray, or scan that will make or confirm a diagnosis of Alzheimer’s. This puts a huge emphasis on accurately detailing the person’s loss of memory and ability to perform daily functions. This presents several challenges. For one, people with Down syndrome typically do not self-report concerns about memory. It is often a caregiver who knows the person well who identifies the changes and then communicates them to the doctor. Secondly, there are other medical conditions commonly associated with Down syndrome that can produce similar symptoms to Alzheimer’s. Conditions that can be mistaken for dementia include thyroid problems, depression, chronic ear and sinus infections, hearing and vision loss, sleep apnea, etc. For this reason, it is important not to rush a diagnosis and to be sure to perform a thorough assessment, considering all other possibilities.
Because of the prevalence of Alzheimer’s among people with Down syndrome, it is necessary to start preparing for the possibility of diagnosis early. The progression of Alzheimer’s is evaluated by comparing the functioning of the person with Alzheimer’s against a baseline measurement of their functioning from when they were healthy. The baseline adult function of a person with Down syndrome should be documented by the time they are 35 years old. Baseline measurements should be taken of their intellectual, behavioral, and social functioning. Good indicators of these functions include basic self-care skills, personal achievements, academic and employment milestones, talents, skills, hobbies, etc. The information should be provided by the person with Down syndrome, a family member, or someone else who is close enough to the person to speak in detail about these items. The person with Down syndrome’s performance in these areas should be regularly monitored and compared to these baselines to look for deviations. Lastly, it may be a good idea to consider seeking a professional assessment by a dementia expert if you are concerned about a loved one. Early symptoms of Alzheimer’s to look out for include:
Reduced interest in being sociable, conversing or expressing thoughts.
Decreased enthusiasm for usual activities.
A decline in the ability to focus.
Sadness, fearfulness or anxiety.
Irritability, uncooperativeness or aggression.
Restlessness or sleep disturbances.
Seizures that begin in adulthood.
Changes in coordination and walking.
Increased noisiness or excitability.
The Alzheimer’s Biomarkers Consortium of Down Syndrome (ABC-DS) is an initiative to identify biomarkers indicating that Alzheimer’s is developing or progressing and track the progression of Alzheimer’s in people with Down syndrome. By analyzing brain imaging scans and blood and tissue samples from adults with Down syndrome and their siblings, the researchers can investigate biomarkers that may provide new information regarding the connection between Alzheimer’s and Down syndrome. It will also help to better understand the course of Alzheimer’s in people with Down syndrome and risk and protective factors. Ideally, this research will benefit people with both conditions and assist in the pursuit of an effective intervention for all people living with Alzheimer’s.
More research must be done to investigate the link between Down syndrome and Alzheimer’s for multiple reasons. People with Down syndrome face overwhelming challenges throughout their lives, and these challenges don’t go away with age. Alzheimer’s is a devastating disease that these people have to live with at disproportionate rates. There is a responsibility to help alleviate this burden. A better understanding of Alzheimer’s in people with Down syndrome could also improve understanding of Alzheimer’s in the general population. Why do some people with Down syndrome get the disease and others don’t? What is the role of the APP gene? Answering these questions could provide helpful insight not only to understanding the link between Down syndrome and Alzheimer’s but understanding Alzheimer’s in the general population as well.