Excess iron could cause Alzheimer’s disease

Alzheimer’s disease (AD) affects millions of people worldwide. There is growing evidence that excessive iron in the brain may contribute to this pathology.

AD is a 𝐧𝐞𝐮𝐫𝐨𝐝𝐞𝐠𝐞𝐧𝐞𝐫𝐚𝐭𝐢𝐯𝐞 𝐝𝐢𝐬𝐞𝐚𝐬𝐞 that is becoming increasingly common as the population ages. It is characterized by the 𝐚𝐜𝐜𝐮𝐦𝐮𝐥𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐚𝐦𝐲𝐥𝐨𝐢𝐝 𝐩𝐥𝐚𝐪𝐮𝐞𝐬 𝐚𝐧𝐝 𝐧𝐞𝐮𝐫𝐨𝐟𝐢𝐛𝐫𝐢𝐥𝐥𝐚𝐫𝐲 𝐭𝐚𝐧𝐠𝐥𝐞𝐬 𝐢𝐧 𝐭𝐡𝐞 𝐛𝐫𝐚𝐢𝐧, leading to inflammation, disruption of neuronal communication, and neuronal death. The mechanisms underlying this pathology are still poorly understood. Studies have shown that 𝐢𝐫𝐨𝐧 𝐚𝐜𝐜𝐮𝐦𝐮𝐥𝐚𝐭𝐢𝐨𝐧 𝐢𝐧 𝐭𝐡𝐞 𝐛𝐫𝐚𝐢𝐧 𝐜𝐚𝐧 𝐢𝐧𝐝𝐮𝐜𝐞 𝐟𝐞𝐫𝐫𝐨𝐩𝐭𝐨𝐬𝐢𝐬, a form of cell death, which can 𝐝𝐞𝐬𝐭𝐫𝐨𝐲 𝐭𝐡𝐞 𝐦𝐢𝐜𝐫𝐨𝐠𝐥𝐢𝐚 essential for brain development.

Microglia have a crucial role in the brain’s immune defense. They ensure the elimination of cellular waster, including the debris of damaged myelin. However, the 𝐞𝐥𝐢𝐦𝐢𝐧𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐦𝐲𝐞𝐥𝐢𝐧 𝐫𝐞𝐥𝐞𝐚𝐬𝐞𝐬 𝐢𝐫𝐨𝐧, which causes ferroptosis when in excess. Ferroptosis is a specific form of 𝐩𝐫𝐨𝐠𝐫𝐚𝐦𝐦𝐞𝐝 𝐜𝐞𝐥𝐥 𝐝𝐞𝐚𝐭𝐡, characterized by the 𝐚𝐜𝐜𝐮𝐦𝐮𝐥𝐚𝐭𝐢𝐨𝐧 𝐨𝐟 𝐢𝐧𝐭𝐫𝐚𝐜𝐞𝐥𝐥𝐮𝐥𝐚𝐫 𝐢𝐫𝐨𝐧 and the concomitant loss of glutathione leading to oxidative lipid damage and ultimately cell death. Therefore, excessive iron in the brain can provoke 𝐦𝐢𝐜𝐫𝐨𝐠𝐥𝐢𝐚 𝐝𝐞𝐠𝐫𝐚𝐝𝐚𝐭𝐢𝐨𝐧 by ferroptosis.

This discovery suggests a 𝐧𝐞𝐰 𝐥𝐢𝐧𝐞 𝐨𝐟 𝐫𝐞𝐬𝐞𝐚𝐫𝐜𝐡 focusing on iron regulation and myelin protection. In addition, these data can be valuable for other diseases such as multiple sclerosis.