A link between Down syndrome and Alzheimer’s disease has been found, and a possible vaccine targets Alzheimer-like characteristics. A study found that individuals with Down syndrome who survive into adulthood face added challenges, like an increased risk of dementia and Alzheimer’s disease.
Down syndrome has many similarities to Alzheimer’s disease, and one of those similarities is that dementia in Down syndrome involves defects in a regulatory enzyme – γ-secretase activating protein (GSAP) – which is similar in Alzheimer’s disease.
The researchers made this conclusion by examining donated brain tissue from deceased Down syndrome individuals, where they uncovered elevated levels of GSAP and its activity. GSAP hyperactivity was also associated with abnormalities in GATA1, which controls GSAP production.
The expression of APP, the key protein in amyloid beta formation, is also extreme in Down syndrome individuals, with four to five times higher in Down syndrome patients, compared to an average brain. “The higher levels of APP in Down syndrome patients causes increased formation of amyloid beta peptides, which then precipitate in the amyloid plaques in the brain much earlier in life. Amyloid plaques begin to form in the brain of Down syndrome patients in the late teens and early 20s,” said lead investigator Dr. Domenico Praticò.
“We’ve shown that GSAP inhibition reduces amyloid production, and because GSAP is specific to the formation of amyloid, without affecting other pathways, it should be a safe alternative to other strategies of a direct γ-secretase inhibition,” Dr. Praticò added.
In people with Down syndrome, vaccine targets Alzheimer-like characteristics
Researchers at the University of California, in collaboration with AC Immune from Switzerland, are testing a vaccine which targets Alzheimer-like characteristics in adults with Down syndrome. Aside from being an abnormality in chromosome 21, Down syndrome also includes gene-regulating expression of amyloid-beta – the main component in Alzheimer’s disease – which clumps together in the brain. There is a higher likelihood of a person with Down syndrome to develop Alzheimer’s disease, compared to a person without Down syndrome.
Researcher William Mobley said, “Persons with Down syndrome represent predictable cases of Alzheimer’s disease. This trial and vaccine offer a dual opportunity. First, it may be a way to modify progression of the disease through anti-amyloid intervention. Second, it should provide important insights about the efficacy and timing of such interventions when targeting sporadic Alzheimer’s disease in the general population.”
“The human trial will focus on safety, tolerability, and immunogenicity of the ACI-24 vaccine. Effects on cognitive function and biomarkers for Alzheimer’s disease will be secondary endpoints,” added principal investigator Michael Rafii.
The upcoming study will involve 24 Down syndrome adults who will receive treatment for 12 months and who will be followed for additional 24 months.
Warning signs of dementia in persons with Down syndrome
Warning signs of dementia in persons with Down syndrome begins with a change in behavior and personality. These changes are different than warning signs seen in Alzheimer’s disease. Changes in personality and behavior may result in loss of empathy, social withdrawal, emotional instability, and apathy.
Some researchers suggest that changes in personality and behavior are similar to that of frontal temporal dementia.
Another warning sign of dementia is if the individual begins to experience seizures when they have no prior history of seizures.
Diagnosis of Alzheimer’s disease in Down syndrome
There are some challenges when trying to diagnose dementia or Alzheimer’s disease in Down syndrome, but there are ways of properly diagnosing a patient. Some means that help diagnose Alzheimer’s disease in Down syndrome patients include:
- Adult baseline function regarding behavior, intellect, and adult abilities should be taken at age 35.
- Close attention should be paid to day-to-day function changes.
- A professional dementia expert should be consulted for an evaluation.
- Other ailments based on the symptoms, such as thyroid problems, depression, and sleep apnea, should be ruled out.
Treat Alzheimer’s in people with Down syndrome
There are no FDA-approved drugs that treat dementia associated with Down syndrome. In other countries, a drug known as cholinesterase inhibitors is used to treat dementia in Down syndrome, but there is not enough evidence to support its effectiveness. Additionally, a common Alzheimer’s drug known as memantine also lacks evidence as a treatment option for dementia in Down syndrome.
Additional research is required in order to develop treatment options for dementia in Down syndrome.
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