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RESEARCHERS SHOW THE IMPORTANCE OF THE LIVER-BRAIN AXIS IN ALZHEIMER'S DISEASE

by Autonomous University of Barcelona

Graphical abstract. Credit: Cells (2023). DOI: 10.3390/cells12111517

A research team from the Universitat Autònoma de Barcelona (UAB) has studied the
livers of Alzheimer's disease mice models and described morphological, cellular,
and functional alterations. In addition, they demonstrated the importance of the
liver-brain axis regarding the psychological symptoms of the disease.





Traditionally, research in Alzheimer's disease has focused exclusively on the
study of the brain alterations that people with this dementia present. However,
there is a hypothesis that oxidative stress and inflammation, accentuated by
aging, may play an important role in the development of the pathology. In this
context, the liver, which is the organ in charge of regulating metabolism and
supporting the immune system, could be a key organ in the development and
prognosis of the disease.

A research team from the UAB Institut de Neurociències, led by Professor Lydia
Giménez-Llort from the UAB Department of Psychiatry and Legal Medicine, in
collaboration with Professor Josep Reig-Vilallonga from the UAB Department of
Morphological Sciences, studied this hypothesis by comparing Alzheimer's disease
mice models and control mice of the same advanced age and sex.

The findings revealed several features of liver dysfunction in the diseased
mice, including hepatomegaly (enlarged liver), histopathological amyloidosis
(abnormal protein deposits in tissues), oxidative stress and cellular
inflammation. The study was published in Cells.

Recently, in another study by the group, researchers highlighted the involvement
of the peripheral organs in this disease, and their importance in the
psychological aspects of the pathology. This new study shows that there are
alterations in the liver-brain axis, which are related to behavioral changes,
such as increased neophobia (fear of novelty), and dysfunctions in the
hypothalamic-pituitary-adrenal axis (HPA), which regulates responses to stress.

"We saw that diseased mice presented larger livers, and when we examined them
under the microscope, we realized they had liver pathology in the form of
amyloidosis. 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," explains Juan Fraile, researcher at the Institut
de Neurociències and first author of the article.



"The histopathological evaluation of the control mice samples also provided new
data regarding the aging process. Hepatic steatosis was the distinguishing
feature in the livers of these animals, and in the male sex it was associated
with obesity," adds Professor Josep Reig-Vilallonga.

The involvement of the liver in the cleaning of the b-amyloid protein, which
accumulates in the brain of Alzheimer's patients, is well-known, as well as the
possible inflammatory communication through pro-inflammatory factors between
these two organs. This is especially important in advanced ages, when the
blood-brain barrier becomes more permeable and allows the periphery and the
brain to be in closer contact.

It is then that the liver, due to its detoxification function, becomes saturated
and increases its inflammation and oxidative stress, which worsens
neuroinflammation and oxidative stress in the nervous system. In addition, apart
from age, the research team demonstrates the influence of sex (male) and
isolation (especially when it is unwanted) on the progression of hepatomegaly,
oxidative stress and inflammation, with the consequent worsening of the
prognosis of the disease.

"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," explains Dr. Giménez-Llort.

The authors conclude that hepatic oxy-inflammation and neophobia represent
potential targets of systems integration in Alzheimer's disease research,
targets that include intrinsic factors, such as genotype and sex, and extrinsic
factors, such as social conditions. The study marks a significant advance in the
understanding of Alzheimer's disease and underlines the need to expand the scope
of research beyond the brain, considering the influence of peripheral organs and
systemic factors.

More information: Juan Fraile-Ramos et al, Hepatic Oxi-Inflammation and
Neophobia as Potential Liver–Brain Axis Targets for Alzheimer's Disease and
Aging, with Strong Sensitivity to Sex, Isolation, and Obesity, Cells (2023).
DOI: 10.3390/cells12111517

Provided by Autonomous University of Barcelona
Citation: Researchers show the importance of the liver-brain axis in Alzheimer's
disease (2023, June 22) retrieved 22 June 2023 from
https://medicalxpress.com/news/2023-06-importance-liver-brain-axis-alzheimer-disease.html
This document is subject to copyright. Apart from any fair dealing for the
purpose of private study or research, no part may be reproduced without the
written permission. The content is provided for information purposes only.

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