Researchers at the USC Leonard Davis School of Gerontology have discovered a strong link between high levels of iron in the brain and increased cell damage in people who have both Down syndrome and Alzheimer’s disease (DSAD).
In their study, the team found that the brains of people with DSAD had twice as much iron and more damage to brain cell membranes compared to people with Alzheimer’s disease alone or those without either condition.
This extra iron appears to trigger a process called ferroptosis — a type of cell death caused by iron that leads to damage in fatty parts of the cell, known as lipids. The results could help explain why people with Down syndrome often develop Alzheimer’s symptoms earlier and more severely than others.
Down syndrome is caused by having an extra copy of chromosome 21, which includes the gene for amyloid precursor protein (APP). This gene is responsible for producing amyloid-beta, a protein that builds up and forms plaques in the brains of people with Alzheimer’s.
Because people with Down syndrome have three copies of the APP gene instead of two, they make more of this protein. By age 60, about half of all individuals with Down syndrome develop signs of Alzheimer’s — around 20 years earlier than the general population.
The researchers examined donated brain tissue from people with DSAD, Alzheimer’s alone, and healthy individuals. They focused on the prefrontal cortex, a part of the brain involved in memory and decision-making.
They found three key differences in DSAD brains:
– Much higher iron levels, likely from small brain vessel leaks called microbleeds
– More damage to lipid-rich membranes due to chemical stress (lipid peroxidation)
– Weaker antioxidant defense systems, especially in areas of the cell membrane called lipid rafts
Lipid rafts are small areas in the brain cell membrane that help with communication between cells and control how proteins like APP are processed.
In DSAD brains, these lipid rafts had more oxidative damage, fewer protective enzymes, and increased activity of an enzyme called β-secretase. This enzyme boosts the production of amyloid-beta, possibly accelerating the growth of plaques and the progression of Alzheimer’s.
The team also looked at rare individuals with mosaic or partial Down syndrome — people who only have the extra chromosome in some of their cells.
These individuals had lower levels of APP and iron in the brain, lived longer, and had less brain damage. This supports the idea that the amount of APP and iron plays a big role in how quickly Alzheimer’s develops.
The findings could lead to new treatment approaches. Early research in mice shows that iron-chelating drugs, which help remove excess iron from the brain, may reduce Alzheimer’s-related damage.
The scientists believe that future therapies may need to focus not just on removing amyloid plaques but also on lowering iron levels and boosting the brain’s natural defenses.
If you care about Alzheimer’s disease, please read studies about These places in U.S. have the most cases of Alzheimer’s disease and findings of Scientists confirm the link between COVID-19 and Alzheimer’s disease.
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