Associations of Serum Liver Function with Cerebral Blood Flow in Patients with Alzheimer's Disease.

Background: Increasing evidence suggests that both amyloid-ß metabolism disorders in the liver and cerebral hypoperfusion play an important role in the pathogenesis of Alzheimer's disease (AD). However, the relevance of liver function alterations to cerebral blood flow (CBF) of patients with AD remains unclear. Objective: We aimed to investigate the associations between liver function changes and CBF of patients with AD. Methods: We recruited 17 patients with sporadic AD. In addition to physical and neurological examinations, detection of AD biomarkers in cerebrospinal fluid by enzyme-linked immunosorbent assay and CBF assessment by arterial spin labeling sequence of magnetic resonance image scans as well as measure of liver function markers in serum by routine laboratory testing were conducted. Neuropsychological tests were evaluated, including Mini-Mental State Examination and Montreal Cognitive Assessment. Linear and rank correlations were performed to test the associations of liver function alterations with regional CBF of AD. Results: We found that liver function markers, especially total protein, the ratio of albumin to globin, globin, alkaline phosphatase, and aspartate aminotransferase were significantly associated with regional CBF of AD patients. Conclusions: These findings demonstrated significant associations between perfusion in certain brain regions of AD and alterations of liver function markers, particularly proteins and liver enzymes, which might provide implications to the pathogenesis and treatment of AD.

Associations of apolipoprotein E ε4 allele, regional cerebral blood flow, and serum liver function markers in patients with cognitive impairment.

Introduction: The ε4 allele of the apolipoprotein E gene (APOE4) is expressed abundantly in both the brain and peripheral circulation as a genetic risk factor for Alzheimer's disease (AD). Cerebral blood flow (CBF) dysfunction is an essential feature of AD, and the liver plays an important role in the pathogenesis of dementia. However, the associations of APOE4 with CBF and liver function markers in patients with cognitive impairment remains unclear. We aimed to evaluate the associations of APOE4 with CBF measured by arterial spin labeling (ASL) magnetic resonance imaging (MRI) and serum liver function markers in participants who were diagnosed with cognitive impairment. Methods: Fourteen participants with AD and sixteen with amnestic mild cognitive impairment (MCI) were recruited. In addition to providing comprehensive clinical information, all patients underwent laboratory tests and MRI. All participants were divided into carriers and noncarriers of the ε4 allele, and T-tests and Mann-Whitney U tests were used to observe the differences between APOE4 carriers and noncarriers in CBF and liver function markers. Results: Regarding regional cerebral blood flow (rCBF), APOE4 carriers showed hyperperfusion in the bilateral occipital cortex, bilateral thalamus, and left precuneus and hypoperfusion in the right lateral temporal cortex when compared with noncarriers. Regarding serum liver function markers, bilirubin levels (including total, direct, and indirect) were lower in APOE4 carriers than in noncarriers. Conclusion: APOE4 exerts a strong effect on CBF dysfunction by inheritance, representing a risk factor for AD. APOE4 may be related to bilirubin metabolism, potentially providing specific neural targets for the diagnosis and treatment of AD.

Comparative Lipidomics and Metabolomics Reveal the Underlying Mechanisms of Taurine in the Alleviation of Nonalcoholic Fatty Liver Disease Using the Aged Laying Hen Model.

SCOPE: Aged laying hen is recently suggested as a more attractive animal model than rodent for studying nonalcoholic fatty liver disease (NAFLD) of humans. This study aims to reveal effects and metabolic regulation mechanisms of taurine alleviating NAFLD by using the aged laying hen model. METHODS AND RESULTS: Liver histomorphology and biochemical indices show 0.02% taurine effectively alleviated fat deposition and liver damage. Comparative liver lipidomics and gene expressions analyses reveal taurine promoted lipolysis, fatty acids oxidation, lipids transport, and reduced oxidative stress in liver. Furthermore, comparative serum metabolomics screen six core metabolites negatively correlated with NAFLD, including linoleic acid, gamma-linolenic acid, pantothenate, L-methionine, 2-methylbutyroylcarnitine, L-carnitine; and two core metabolites positively correlated with NAFLD, including lysophosphatidylcholine (14:0/0:0) and lysophosphatidylcholine (16:0/0:0). Metabolic pathway analysis reveals taurine mainly regulated linoleic acid metabolism, cysteine and methionine metabolism, carnitine metabolism, pantothenic acid and coenzyme A biosynthesis metabolism, and glycerophospholipid metabolism to up-adjust levels of six negatively correlated metabolites and down-adjust two positively correlated metabolites for alleviating NAFLD of aged hens. CONCLUSION: This study firstly reveals underlying metabolic mechanisms of taurine alleviating NAFLD using the aged hen model, thereby laying the foundation for taurine's application in the prevention of NAFLD in both human and poultry.

A quantitative analysis framework of placenta accreta spectrum: placenta subtype, intraoperative bleeding, and hysterectomy risk evaluation based on magnetic resonance imaging-anatomical-clinical features.

Background: Placenta accreta spectrum (PAS) is a significant contributor to maternal morbidity and mortality. Our objective was to develop a quantitative analysis framework utilizing magnetic resonance imaging (MRI)-anatomical-clinical features to predict 3 clinically significant parameters in patients with PAS: placenta subtype (invasive vs. non-invasive placenta), intraoperative bleeding (≥1,500 vs. <1,500 mL), and hysterectomy risk (hysterectomy vs. non-hysterectomy). Methods: A total of 125 pregnant women with PAS from 2 medical centers were enrolled into an internal training set and an external testing set. Some 21 MRI-anatomical-clinical features were integrated as input into the framework. The proposed quantitative analytic framework contains mainly 3 classifiers built by extreme gradient boosting (XGBoost) and their testing in external datasets. We also further compared the accuracy of placenta subtype prediction between the proposed model and 4 radiologists. A quantitative model interpretation method called SHapley Additive exPlanations (SHAP) was conducted to explore the contribution of each feature. Results: The placenta subtype (invasive vs. non-invasive), intraoperative bleeding (≥1,500 vs. <1,500 mL), and hysterectomy risk (hysterectomy vs. non-hysterectomy) demonstrated impressive area under the receiver operating characteristic curve (AUROC) values of 0.93, 0.88, and 0.90, respectively, in the internal validation set. Even in the external testing set, these metrics maintained their strength, achieving AUROC values of 0.91, 0.82, and 0.82, respectively. Comparing our proposed framework to the 4 radiologists, our model exhibited superior accuracy, specificity, and sensitivity in predicting placental subtypes within the external testing cohort. The features associated with intraplacental dark T2 bands played a crucial role in the decision-making process of all 3 prediction models. Conclusions: The quantitative analysis framework can provide a robust method for classification of placenta subtype (invasive vs. non-invasive placenta), intraoperative bleeding (≥1,500 vs. <1,500 mL), and hysterectomy risk (hysterectomy vs. non-hysterectomy) based on MRI-anatomical-clinical features in PAS.