The livers of Alzheimer’s disease mouse models have been studied by researchers from the Universitat Autnoma de Barcelona (UAB) and morphological, cellular, and functional changes have been observed. They also demonstrated the significance of the liver-brain axis in relation to the disease’s psychological symptoms.
Alzheimer’s disease research has traditionally concentrated solely on examining the brain changes that people with the disease exhibit. However, it is possible that oxidative stress and inflammation, which are made worse by aging, contributed significantly to the pathology’s emergence. In this context, the liver, which is in charge of regulating metabolism and assisting the immune system, may play a significant role in the disease’s development and outlook.

By comparing models of Alzheimer’s disease and control mice of the same advanced age and sex, a research team from the UAB Institut de Neurociencies, led by Professor Lydia Giménez-Llort from the UAB Department of Psychiatry and Legal Medicine, and Professor Josep Reig-Vilallonga from the UAB Department of Morphological Sciences investigated this hypothesis.

Hepatomegaly, which is an enlarged liver, histopathological amyloidosis, which is abnormal protein deposits in tissues, oxidative stress, and cellular inflammation were all found in the diseased mice, according to the findings. Cells is where the study was published.

Peripheral organ involvement in this disease and their significance in the psychological aspects of the pathology were recently highlighted in another group study. This new study demonstrates that dysfunctions in the hypothalamic-pituitary-adrenal axis (HPA), which regulates responses to stress, and alterations in the liver-brain axis are linked to behavioral changes like increased neophobia (fear of novelty).

“When we examined diseased mice under the microscope, we discovered that they had liver pathology in the form of amyloidosis. We noticed that diseased mice had larger livers. As a result, Juan Fraile, a researcher at the Institut de Neurociencies and the first author of the article, explains, “We decided to deepen the study of the alterations that could be occurring in the liver and in the liver-brain relationship, which has been rarely studied until now.”

“New information regarding the aging process was also obtained from the histopathological examination of the control mouse samples. Professor Josep Reig-Vilallonga adds, “Hepatic steatosis was the distinguishing feature in the livers of these animals, and it was associated with obesity in the male sex.”

It is common knowledge that the liver cleans the b-amyloid protein that builds up in Alzheimer’s patients’ brains. It is also possible that these two organs can communicate with inflammation through pro-inflammatory factors. This is particularly significant in old ages, when the blood-mind obstruction turns out to be more penetrable and permits the fringe and the cerebrum to be in nearer contact.

It is then that the liver, because of its detoxification capability, becomes soaked and builds its irritation and oxidative pressure, which deteriorates neuroinflammation and oxidative pressure in the sensory system. In addition, the research team demonstrates that, in addition to age, sex (male) and isolation—especially when unwelcome—have an impact on the progression of hepatomegaly, oxidative stress, and inflammation, which in turn has a negative impact on the disease’s prognosis.

According to Dr. Giménez-Llort, “the liver-brain axis alterations and liver dysfunction observed in the diseased animals in our study open new paths to understanding the systemic aspects of this complex disease” and “help identify potential targets for further research, including the perspective of sex/gender and the impact of loneliness.”

The authors come to the conclusion that in Alzheimer’s disease research, hepatic oxy-inflammation and neophobia are potential targets for systems integration. These targets include intrinsic factors like genotype and sex and extrinsic factors like social conditions. The study highlights the necessity of expanding the scope of research beyond the brain to include the influence of peripheral organs and systemic factors. It also represents a significant advance in our understanding of Alzheimer’s disease.