A study published in the journal Alzheimer’s & Dementia analyzed how excess iron in the brain promotes Alzheimer’s disease, particularly in people with Down syndrome. Researchers studied brain tissue from three groups: healthy adults, adults with Alzheimer ‘s , and adults with Alzheimer’s related to Down syndrome. Their goal was to understand how iron accumulation damages brain cells and causes the buildup of sticky proteins called amyloid plaques, which are associated with Alzheimer’s.
• Iron levels were much higher in people with Down syndrome and Alzheimer’s: compared to healthy adults and those with Alzheimer’s alone, people with both conditions had almost twice as much iron in an important brain region responsible for memory and decision-making.
This group showed much higher levels of damage because iron reacts with fats in brain cells and breaks them down. Furthermore, the natural defenses that protect brain cells from this type of damage were weakened or absent.
• Protective brain enzymes were lacking where they were most needed: The study found that enzymes that typically repair damage to brain cell membranes were reduced by up to 70% in the affected areas. These enzymes are important because they help prevent brain cell death caused by iron overload.
Glutathione, another protective compound, was also not produced correctly. This is because the enzyme needed to produce it was also reduced by up to 60%. Without sufficient glutathione levels, brain cells lose an important line of defense against stress and oxidation.
• Iron damaged important parts of brain cells that act as control centers: The study found that iron attacked small areas on the cell surface where important proteins are processed and messages are sent. In brains affected by Alzheimer’s (especially in people with Down syndrome), these areas were severely damaged. This damage changed the way certain proteins are made, increasing the toxic forms that clump together in the brain and destroy nerve cells.
Are small brain hemorrhages the source of excess iron?
An important clue came from the discovery of iron deposits in areas associated with microscopic bleeding. These “microhemorrhages” are tiny leaks from blood vessels in the brain that often go unnoticed. When blood seeps into brain tissue, it breaks down and releases iron.
Over time, this creates pockets of stored iron that cause further damage. The study found that a clearing enzyme, which helps process iron in the blood, was three times higher in the brains of people with Down syndrome and Alzheimer’s, suggesting that chronic bleeding led to iron overload.
• The brain’s protein-cutting process became more destructive under stress: Normally, certain brain proteins can be cut in ways that are either safe or harmful. The harmful cutting process became more active in damaged brains, not because there was more of the cutting enzyme, but because it worked faster, perhaps due to iron-related stress. At the same time, the safer cutting process slowed down. This change caused the brain to produce more toxic proteins instead of removing them.
Although the body produced more antioxidants, they weren’t in the right place: the brain as a whole appeared to increase levels of antioxidant enzymes in response to the damage, but those enzymes weren’t where they were most needed. This mismatch meant that cells were still vulnerable to damage, even as the body tried to defend itself. It was shown that the damage caused by Alzheimer’s is not limited to general inflammation or oxidation, but rather involves damage occurring in specific, high-risk areas.
Genes influence the amount of iron that accumulates in the brain: in people with rare forms of Down syndrome who did not have an extra copy of a certain protein-producing gene, there was much less iron in the brain, fewer build-ups of harmful proteins, and they lived up to 20 years longer than people with the extra gene. This shows that producing too much of that protein leads to greater iron accumulation, more brain damage, and a shorter lifespan, helping to explain why some people’s brains deteriorate faster than others’.
