The Impact of Iron Levels on Brain Degeneration in Down Syndrome-Related Alzheimer's Disease

Recent research from the USC Leonard Davis School of Gerontology highlights a significant link between elevated iron concentrations in the brain and heightened cellular damage in individuals with both Down syndrome and Alzheimer's disease. Scientists discovered that brains from these individuals contain twice the amount of iron and exhibit greater signs of oxidative damage in cell membranes compared to those with only Alzheimer's or healthy controls.

The study, published in Alzheimer's & Dementia, revealed that increased iron may contribute to a specific pathway of cell death called ferroptosis, characterized by iron-dependent lipid peroxidation that damages cell membranes. This process appears to be more prominent in the prefrontal cortex, a vital brain region involved in cognition, memory, and decision-making.

Researchers observed that lipid rafts—small domains within brain cell membranes crucial for signaling and protein processing—showed increased oxidative damage and higher activity of β-secretase enzyme, which facilitates the production of amyloid-beta plaques. These plaques are hallmark features of Alzheimer's pathology and tend to develop earlier and more aggressively in people with Down syndrome.

Further analysis of individuals with mosaic or partial trisomy 21, where only some cells carry the extra chromosome, indicated lower levels of iron and APP protein, correlating with longer lifespans and reduced brain damage. These findings suggest that both APP and its associated iron accumulation play a critical role in disease progression.

The implications of this research point towards potential therapeutic strategies, such as iron-chelating treatments and antioxidants, aiming to reduce iron buildup and oxidative stress in the brain. Such approaches could slow or prevent the onset of Alzheimer's in vulnerable populations, particularly those with Down syndrome, by targeting the underlying mechanisms of ferroptosis.

This discovery enhances our understanding of how excess iron contributes to neurodegeneration and opens new avenues for targeted interventions, possibly delaying or mitigating Alzheimer's symptoms in high-risk groups.

Source: https://medicalxpress.com/news/2025-06-iron-play-major-role-syndrome.html