Link Between Down Syndrome and Alzheimer's Disease, and Their Occurrence Rates
In individuals with Down syndrome (DS), there is an increased risk of developing Alzheimer's disease (AD). This heightened risk is primarily linked to the triplication of the APP gene on chromosome 21.
People with DS have an extra copy of chromosome 21, which includes the amyloid precursor protein (APP) gene. This extra copy results in a 50% increase in APP expression, leading to increased production and accumulation of amyloid-beta (Aβ) peptides, particularly Aβ42, which are central to AD pathology.
The overexpression of APP leads to early and nearly universal development of AD neuropathology in individuals with DS. Most develop AD pathology by age 40, and about 70% are diagnosed with dementia by age 54, giving a lifetime AD risk of approximately 95%.
The accumulation of amyloid plaques in the brain, a hallmark of AD, induces neurodegeneration and cognitive decline. Evidence supporting this link includes familial AD mutations in APP that can cause AD even without DS, demonstrating APP's key role.
CRISPR/Cas9 experiments that normalize APP dosage in DS-derived cells reverse neurogenesis defects and AD-like phenotypes, further indicating causality between APP overexpression and AD pathology in DS.
The similarity in clinical symptoms and biomarker changes in DS-related AD and other genetically determined forms of AD highlights APP triplication as a genetically determined driver of AD in DS.
By the age of 60, around 60% of people with Down syndrome have developed clinical symptoms of Alzheimer's disease. The disease progresses through three stages: early, middle, and late.
In the early stage, people may experience mild cognitive changes and memory problems, reduced interest in social interactions, decreased enthusiasm for activities, feelings of sadness, anxiety, and fear. Restlessness and sleep disturbances might also become apparent. Early signs might also include seizures, alterations in coordination and walking, and heightened noisiness or excitability.
In the middle stage, cognitive decline becomes more evident, and memory loss and communication difficulties worsen. Behavioral and personality changes may be more apparent, while assistance with daily activities is usually necessary.
In the late stage, severe cognitive and functional impairment occurs, and people may require full assistance with daily activities, as they might have difficulty with mobility, communication, and self-care. Physical health issues may also become more prevalent.
While there is no surefire way to eliminate the risk of developing AD for people with DS, certain lifestyle factors and interventions may help lower the risk or delay its onset. Regular medical checkups and screenings can help detect any changes or early signs of cognitive decline.
It's crucial to raise awareness about this genetic link and the early signs of AD in individuals with DS to ensure timely diagnosis and intervention, improving their quality of life.
- The triplication of the APP gene on chromosome 21, a genetic characteristic found in individuals with Down syndrome (DS), plays a crucial role in the increased risk of developing Alzheimer's disease (AD).
- People with DS, due to the contextual overexpression of the amyloid precursor protein (APP) gene, have a 50% increase in APP expression, leading to cognitive decline and an early and nearly universal development of AD neuropathology.
- Paxlovid, a medication currently used in other medical conditions, has not been studied or approved for use in addressing dementia or neurological disorders associated with Down syndrome.
- Retargeting interventional strategies, such as using CRISPR/Cas9 to normalize APP dosage, can reverse neurogenesis defects and AD-like phenotypes in DS-derived cells, suggesting a causality between APP overexpression and AD pathology.
- In the scientific community, there is growing evidence that Down syndrome (DS) and Alzheimer's disease (AD) share similar clinical symptoms and biomarker changes, underlining APP triplication as a genetically determined driver of AD in DS.
- The science of mental health, health-and-wellness, and neurodevelopmental disorders should consider focusing research and resources on developing targeted interventions to address the high risk of AD and other dementia-related syndromes in individuals with Down syndrome.
