APOE4 Variant May Increase Inflammation in Early Alzheimer's Disease

The APOE4 variant gene is robustly linked to an increased risk of Alzheimer's disease. Separately, Alzheimer's disease has a clear inflammatory component, to the point at which some groups hypothesize that chronic inflammation is the important driving mechanism of the condition. Here, researchers report on evidence linking the APOE4 variant to greater induction of inflammation related to the presence of amyloid-β aggregates in the brain.

Alzheimer's disease is characterised by the accumulation of plaques of the amyloid-β protein, chronic inflammation and impaired neuronal function in the brain. The most significant genetic risk factor for the disease is apoE4, a variant of apolipoprotein E, which is known for, among other things, advancing the onset of the disease. While more than half of all individuals with Alzheimer's disease carry this variant, the exact effect of apoE4 on the development of the disease has remained unknown.

A new study identified a more accurate link between the apoE4 gene and the part of the human body's immune system that underlies, among other things, Alzheimer's disease. This is known as the complement system, and it contributes to the destruction of foreign cells and easily triggers inflammatory responses in the body. "We found that apoE4 poorly binds factor H, a regulatory factor of immunity. The factor H molecule is crucial in preventing complement-mediated inflammation. Usually, apoE binds factor H to the amyloid-β aggregates in the brain, thus reducing local inflammation. But apoE4 does not. This results in the accumulation of harmful amyloid-β aggregates and inflammation in the brain."

Link: https://www.helsinki.fi/en/news/brain/new-information-development-alzheimers-disease-study-reveals-possible-cause-inflammation

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