The liver-brain axis is crucial to Alzheimer’s disease

Summary: The liver may play a crucial role in the progression of Alzheimer’s disease, according to research.

The study found abnormal protein deposits and oxidative stress in Alzheimer’s disease mouse models of liver dysfunction. These results suggest that changes in behavior and stress responses alter the liver-brain axis.

The findings indicate the significance of systemic factors and peripheral organs in Alzheimer’s disease diagnosis and treatment.

Key Realities:

The study found a link between liver dysfunction, such as enlarged liver, abnormal protein deposits, and oxidative stress, and Alzheimer’s disease.
Alzheimer’s patients’ behavioral changes and dysfunctions in the stress response may be linked to changes in the liver-brain axis.
Peripheral organs and systemic factors, like age, sex, and isolation, are important for understanding and treating Alzheimer’s disease, according to the study.
Source: UAB Traditionally, Alzheimer’s disease research has primarily focused on the brain changes that people with the disease experience.

However, it is possible that oxidative stress and inflammation, which are made worse by aging, contributed significantly to the pathology’s emergence. The liver, which is in charge of regulating metabolism and supporting the immune system, may play a significant role in its development and prognosis in this context.

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.

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.

Juan Fraile, a researcher at the Institut de Neurociencies and the first author of the article, with which he begins his PhD, explains, “That is why 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.” “The histopathological evaluation of the control mice samples also provided new data regarding the aging process.” Professor Josep Reig-Vilallonga adds, “Hepatic steatosis was the distinguishing feature in the livers of these animals, and in the male sex it was associated with obesity.”

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 talk to each other about inflammation through pro-inflammatory factors.

This is especially crucial as we get older because the blood-brain barrier becomes more permeable, allowing the brain and the periphery to come closer together. The liver becomes saturated as a result of its detoxification function, which worsens neuroinflammation and oxidative stress in the nervous system and increases inflammation and oxidative stress.

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.

Dr. Giménez-Llort elaborates, “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 facilitate the identification of potential targets for further research, including the perspective of sex/gender and the impact of loneliness.” “The liver-brain axis alterations and liver dysfunction observed in the diseased animals in our study”

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.

As Potential Liver-Brain Axis Targets for Alzheimer’s Disease and Aging, with Strong Sensitivity to Sex, Isolation, and Obesity, Hepatic Oxi-Inflammation and Neophobia Research on Alzheimer’s disease (AD) has traditionally focused on the changes that take place in the brain and the intra- and extracellular neuropathological hallmarks that go along with them.

However, the oxi-inflammation hypothesis of aging may also play a role in neuroimmunoendocrine dysregulation and the pathophysiology of the disease. Due to its role in regulating metabolism and supporting the immune system, the liver emerges as a target organ in this hypothesis. Hepatocellular oxidative stress (decreased glutathione peroxidase and increased glutathione reductase enzymatic activities) and inflammation (increased IL-6 and TNF) are characterized as hallmarks of hepatic dysfunction in 16-month-old male and female 3xTg-AD mice at advanced stages of the disease in comparison to age- and sex-matched non-transgenic (NTg) counterparts in the current study.

In addition, behavioral (increased neophobia) and HPA axis correlations that were enhanced under forced isolation revealed alterations in the liver–brain axis.

Sex (male) and natural or forced isolation were all associated with worse hepatomegaly, oxidative stress, and inflammation progression in all cases. Additionally, older male NTg mice with obesity had a higher steatosis grade.

More research is being done to see if these changes could be linked to a worse prognosis for the disease and to identify integrative system targets for AD research.