Why People with Down Syndrome are at High Risk for Alzheimer’s Disease

Down syndrome is a neurodevelopmental disorder caused by inheriting an extra copy of chromosome 21. The most common symptoms include intellectual disability, unusual facial features, and heart defects. About 1 in 700 babies is born with this condition.

The average lifespan for a person with Down syndrome is 60 years. Sadly, the last few years of their lives are often lost to Alzheimer’s disease. Nearly two-thirds of Down syndrome patients are diagnosed with Alzheimer’s before the age of 60. This is far higher than the general population, of whom less than 1% develop Alzheimer’s this early in life.

The reason for this greatly elevated risk of Alzheimer’s disease comes down to genetics. While chromosome 21 contains hundreds of different genes, a single gene is believed to cause Alzheimer’s disease in Down syndrome patients: APP. This gene encodes a protein called amyloid-beta. Amyloid-beta is a toxic, sticky protein that can clump together and accumulate inside the brain, which is believed to be a major contributing factor to Alzheimer’s disease.

Because of their extra copy of chromosome 21, people with Down syndrome produce more amyloid-beta than normal. Nearly 100% of Down syndrome patients start to develop amyloid-beta aggregates in their brains during their 40s. This puts them at a very high risk of developing Alzheimer’s at an early age.

After the practice of institutionalizing people with Down syndrome became less common, their life expectancy improved dramatically, up from only 25 in 1983 to 60 today. However, this means that more Down syndrome patients are living long enough to develop Alzheimer’s disease, which is a frightening prospect to these individuals and their families.

Despite the troubling statistics, there is hope for people with Down syndrome. Many neuroscientists believe that early intervention is key for preventing Alzheimer’s disease. However, ethical standards make it difficult to administer treatments to people before we know for sure that they’ll develop a disease, particularly if those treatments come with certain risks. This makes it challenging to test out new preventative therapies for Alzheimer’s disease.

Because of the very high rate of Alzheimer’s disease among Down syndrome patients, they may be an exception to this rule. New drug candidates can be tested on these individuals beginning early in life, which may prove to be a more effective strategy for preventing Alzheimer’s. While only time can tell whether these treatments will prove beneficial, many remain hopeful for the future of research.


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2 thoughts on “Why People with Down Syndrome are at High Risk for Alzheimer’s Disease

  1. Stephen Robinson

    The link between Down Syndrome and Alzheimer’s disease (AD) is an intriguing one. Proponents of the Amyloid Cascade Hypothesis have often cited the high incidence of premature AD-like dementia in Down Syndrome as proof that beta amyloid causes AD. They reason that the extra copy of the gene that codes for amyloid precursor protein (APP) will increase the rate of synthesis of beta amyloid, and hasten the onset of AD. However, this line of reasoning overlooks the fact that an entire chromosome has been triplicated, resulting in a complicated phenotype that affects many systems, one of which the immune system.

    There is a fascinating link between Down Syndrome and infections: “DS individuals may have a high frequency of infections, usually of the upper respiratory tract, characterized by increased severity and prolonged course of disease, which are partially attributed to defects of the immune system. The abnormalities of the immune system associated with DS include: mild to moderate T and B cell lymphopenia, with marked decrease of naive lymphocytes, impaired mitogen-induced T cell proliferation, reduced specific antibody responses to immunizations and defects of neutrophil chemotaxis.” (Ram and Chinen, 2011; https://www.ncbi.nlm.nih.gov/pubmed/21352207).

    There is also an interesting negative association with cancer: “renal carcinoma, small cell lung carcinoma, and malignant melanoma, are less frequent in adults with DS compared to the general population. Thus, despite the combination of an increased risk of leukemia with detectable immune biological abnormalities and a clinical immunodeficiency, people with DS appear to be protected against many cancers.” (Satge and Seidel, 2018; https://www.ncbi.nlm.nih.gov/pubmed/30631328).

    Liked by 1 person

  2. Alice Gosztyla

    Very interesting; I knew that the rate of Alz among people with Down’s Syndrome was higher, but I did not know that it was over 60%. That is sad, but also possibly another route for study into this disease. Thank you.



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