MEDICINE AND HEALTH

The latest study found that the liver is involved in the onset of Alzheimer’s disease


On July 3, “Neurons” published the latest results of Zhu Xinhong’s team in the field of pathogenesis and prevention of Alzheimer’s disease with the title of “Hepatic soluble epoxide hydrolase activity regulates Aβ metabolism in the brain and mediates the pathogenesis of senile dementia”.

Neuroprotective role of the liver in aging and Alzheimer’s disease. Photo courtesy of the research team

Previous studies on the pathogenesis of Alzheimer’s disease have mostly focused on the central nervous system. However, in recent years, studies have found that peripheral organs (tissues) play an important role in maintaining normal brain function and the pathogenesis of brain diseases. Alzheimer’s disease is a complex disease in which genetic and environmental factors interact, and elucidating the role of peripheral organs (tissues) in the pathogenesis of Alzheimer’s disease may provide new strategies for Alzheimer’s disease prevention and treatment.

The study found that the liver was involved in the onset of Alzheimer’s disease: the enzymatic activity of hepatic soluble epoxide hydrolase (sEH) gradually increased with age; The plasma level of 14,15-epoxyeicosatrienoic acid (14,15-EET) decreased progressively; In a mouse model of Alzheimer’s disease, specific regulation of hepatic sEH enzyme activity can bidirectionally regulate the production and deposition of beta-amyloid (Aβ) in the brain and regulate the phosphorylation level of Tau protein, thereby regulating cognitive and behavioral deficits.

In addition, hepatic sEH enzyme activity specifically regulates plasma 14,15-EET levels; 14,15-EET can quickly cross the blood-brain barrier and regulate Aβ metabolism in the brain through multiple pathways; An imbalance between 14,15-EET and Aβ levels in the brain is a prerequisite for the occurrence of Aβ deposition. Targeted liver sEH recombinant adeno-associated virus therapy can reverse the pathological process of Alzheimer’s mouse models, improve cognitive behavior, and provide new ideas for the treatment of Alzheimer’s disease. In particular, based on the detection of blood 14,15-EET levels in Alzheimer’s patients and healthy control groups, it is suggested that the reduction of plasma 14,15-EET levels can predict the onset of Alzheimer’s disease, with high sensitivity and specificity, and provide scientific basis for early warning of Alzheimer’s disease.

This study innovatively elucidates the role of the liver in regulating brain Aβ metabolism for the first time, discovers the potential possibility of targeting the liver for the treatment of Alzheimer’s disease, and provides a new strategy for the prevention and treatment of Alzheimer’s disease. (Source: China Science News Zhu Hanbin)

Related paper information:https://doi.org/10.1016/j.neuron.2023.06.002



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