■阿尔茨海默病(AD)是一种复杂的神经退行性疾病,受多种因素的影响,包括肝功能,这可能会影响大脑中淀粉样蛋白β(Aβ)的清除。本研究旨在探讨载脂蛋白E(APOE)ε4等位基因如何影响肝功能标志物与AD病理和认知的关系。
■我们分析了来自两个独立队列的数据,包括来自哈勒姆大学医学中心的732名参与者和来自阿尔茨海默病神经影像学倡议的483名参与者,每组由具有和不具有APOEε4等位基因的个体组成。横断面分析评估了肝酶的关联(天冬氨酸转氨酶[AST],丙氨酸转氨酶[ALT],碱性磷酸酶,总胆红素,和白蛋白)与AD诊断,淀粉样蛋白正电子发射断层扫描(PET)负荷,和AD的脑脊液生物标志物(Aβ42,总tau,和磷酸化的tau181)在基线。纵向,我们调查了一年中这些肝酶与认知能力变化之间的关联.使用Logistic和线性回归模型来分析这些关联,并进行中介分析以评估年龄和淀粉样蛋白PET负荷是否介导了这些关联。
■仅在APOEε4载波组中,高AST与ALT比率和低ALT水平与AD诊断显着相关,淀粉样蛋白PET负荷增加,两个队列中认知功能的纵向下降更快。特别是,在阿尔茨海默病神经影像学计划队列中,AST与ALT比值仅与APOEε4载体组的脑脊液Aβ42水平相关,但与磷酸化tau181或总tau水平无关.此外,来自两个队列的中介分析显示,在APOEε4携带者组中,年龄并不介导肝酶与AD诊断或淀粉样蛋白PET负荷之间的关联.然而,淀粉样蛋白PET负荷仅在APOEε4携带者组中部分介导了肝酶与AD诊断之间的关联。
■这项研究为APOEε4等位基因与肝酶的显着关联及其在AD中与Aβ相关的发病机理和认知中的潜在作用提供了有价值的见解。需要进一步的研究来阐明这些发现的潜在机制和潜在的治疗意义。
UNASSIGNED: Alzheimer\'s disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-β (Aβ) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele affects the relationship of liver function markers with AD pathology and cognition.
UNASSIGNED: We analyzed data from two independent cohorts, including 732 participants from the Hallym University Medical Center and 483 from the Alzheimer\'s Disease Neuroimaging Initiative, each group consisting of individuals with and without the APOE ε4 allele. Cross-sectional analyses evaluated the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, and cerebrospinal fluid biomarkers for AD (Aβ42, total tau, and phosphorylated tau181) at baseline. Longitudinally, we investigated the associations between these liver enzymes and changes in cognitive performance over the course of a year. Logistic and linear regression models were used to analyze these associations and mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations.
UNASSIGNED: Only in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, and faster longitudinal decline in cognitive function in both cohorts. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aβ42 levels exclusively in the APOE ε4 carrier group in the Alzheimer\'s Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses from both cohorts revealed that in the APOE ε4 carriers group, age did not mediate the associations between liver enzymes and AD diagnosis or amyloid PET burden. However, amyloid PET burden partially mediated the association between liver enzymes and AD diagnosis exclusively in the APOE ε4 carriers group.
UNASSIGNED: This study provides valuable insights into the significant association of the APOE ε4 allele with liver enzymes and their potential role in Aβ-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.