Around 1 in 800 people are born with Down syndrome, and by the time they reach their 60s, about two-thirds of them will have early-onset Alzheimer’s, according to figures cited by the Francis Crick Institute. A disability charity’s guide puts the number higher, saying roughly 70 to 80 percent of adults with Down syndrome show cognitive decline consistent with Alzheimer’s by age 65.
The reason starts with chromosome 21. People with Down syndrome carry an extra copy of it, and that chromosome holds the gene for amyloid precursor protein, or APP. More APP means more amyloid-beta, the protein that clumps into sticky plaques in the brains of people with Alzheimer’s. Those plaques disrupt communication between nerve cells and set off inflammation.
Years before symptoms
The brain changes come early. Many adults with Down syndrome have the same plaques seen in older Alzheimer’s patients by their 40s, and some start developing them in their 30s, well before any symptoms show. Not everyone with plaques shows signs right away. Oxidative stress, mitochondrial dysfunction and inflammation are thought to add to the risk, and chromosome 21 also carries genes that help control the immune system.
Not just one gene
For years APP was the prime suspect among the 231 genes on chromosome 21. Researchers at the Francis Crick Institute tested that in 2018 using mouse models. Mice carrying an extra copy of all the human chromosome 21 genes had more amyloid-beta and more plaques in a memory-related part of the brain, and did worse on memory tests. They also made more of a form of amyloid-beta that clumps easily.
“We’ve shown for the first time that genes other than APP are playing a role in early-onset Alzheimer’s disease in our model of Down Syndrome,” said Frances Wiseman, the study’s first author. Finding those genes, she said, could one day let doctors “intervene with these pathways to prevent the disease.”
Victor Tybulewicz, a senior author, noted that Down syndrome is hard to model in mice because the genes found on chromosome 21 in humans are spread across three different mouse chromosomes.
Trials under way
There is still no cure. Studies are testing options, though. The ABATE trial is looking at whether an anti-amyloid drug, Kisunla, is safe and works in this group. The Trial-Ready Cohort-Down Syndrome project is enrolling adults without symptoms to find early biomarkers and test treatments before decline begins. Brain scans and spinal fluid tests can already show amyloid and tau changes before symptoms appear.
The charity’s guide lists early warning signs families can watch for: trouble adapting to new places, sudden loss of interest in favorite hobbies, less attention to personal hygiene, and difficulty recognizing familiar faces. Anyone who notices changes in a loved one should talk to a doctor, and the research above gives families real reason for hope.
Sources
- Down Syndrome and Alzheimer’s: Understanding the Connection
- Genes linking Alzheimer’s to Down syndrome found, to help early diagnosis
