Liver-Brain Axis in Sporadic Alzheimer’s Disease: Role of Ten Signature Genes in a Mouse Model

Abstract

Aim:: Poor nutritional effect of junk food induces injurious adversities to the liver and brain but still most of the developing nations survives on these diets to compensate for fast-paced lifestyle. Aim of the study is to infer the proteinconnections behind liver-brain axis and identify the role of these proteins in causing neurodegenerative disorders. Background: : Chronic consumption of fructose and fat rich food works as a toxin in body and have the ability to cause negative metabolic shift. Recently a study was published in Annals of Internal Medicine (2019) citing the loss of vision and hearing in a 14-year-old boy whose diet was strictly restricted to fries and junk-food for almost a decade. This puts the entire body on insulin resistance and related co-morbidities and causes simultaneous damaging effects in liver as well brain. This work provides insights into liver-brain axis and explains how liver is involved in brain related disorders. Objective: : In this study transcriptomic data relating to chronic eating of junk-food was analyzed and simultaneous damage that happens in liver and brain was assessed at molecular level. Method:: Transcriptomic study was taken from GEO database and analysed to find out the genes dysregulated in both liver and brain during this metabolic stress. Cytoscapev3.7 was used to decipher the signalling between liver and brain. This connection between both was called as Liver-Brain axis. Results : The results obtained from our study indicates the role of TUBB5-HYOU1-SDF2L1-DECR1-CDH1-EGFR-SKP2- SOD1-IRAK1-FOXO1 gene signature towards the decline of concurrent liver and brain health. Dysregulated levels of these genes are linked to molecular processes like cellular senescence, hypoxia, glutathione synthesis, amino acid modification, increased nitrogen content, synthesis of BCAAs, cholesterol biosynthesis, steroid hormone signalling and VEGF pathway. Conclusion: We strongly advocate that prolonged consumption of junk food is a major culprit in brain related disorders like Alzheimer’s disease and propose that receptors for brain diseases lie outside the brain and aiming them for drug discovery and design may be beneficial in future clinical studies. This study also discusses the connection between NAFLD (nonalcoholic fatty liver disease) and sAD (sporadic Alzheimer’s disease) owing to liver-brain axis.

Machine Learning Analysis Reveals Biomarkers for the Detection of Neurological Diseases

“…In addition to the promising true positive rate, inspection of the model weights correctly identified directional trends in blood and urine biochemistry and cognitive function that confirm previous reports in the literature. These included biomarkers which are normally associated with liver disease, such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), and bilirubin, confirming the possibility of a role for the liver-brain axis in NLDs such as AD, as previously reported (Bassendine et al, 2020 ; Jakhmola-Mani et al, 2021 ).…”

Peripheral blood amyloid-β involved in the pathogenesis of Alzheimer’s disease via impacting on peripheral innate immune cells

“…During Aβ pathology progression [ 33 ], the liver was the major organ responsible for plasma clearance of Aβ 40/42 [ 34 , 35 ]. In our recent study, we found that the liver weights of APP/PS-1 transgenic (Tg) mice, the animal model for AD, decreased significantly, and liver cell necrosis as well as lymphocyte infiltration increased obviously compared to wild type mice [ 36 ], which indicates that the liver plays important roles in the pathogenesis of AD through affecting on Aβ metabolism [ 32 , 37 , 38 ]. Other peripheral sources of Aβ are endothelial vascular cells [ 39 ] and skeletal muscle [ 40 , 41 ], but they are not the main source of the peripheral blood Aβ.…”

Intravenous MSC-Treatment Improves Impaired Brain Functions in the R6/2 Mouse Model of Huntington’s Disease via Recovered Hepatic Pathological Changes

“…Recent studies propose that the liver impacts the risk and progression of neurodegenerative disorders [ 16 , 17 , 18 , 19 ]. As the peripheral organs and the central nervous system (CNS) bidirectionally communicate, changes in one can influence the other.…”