Liver as a new target organ in Alzheimer's disease: insight from cholesterol metabolism and its role in amyloid-beta clearance.

Neural Regen Res

Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

Published: March 2025

Alzheimer's disease, the primary cause of dementia, is characterized by neuropathologies, such as amyloid plaques, synaptic and neuronal degeneration, and neurofibrillary tangles. Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs, targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment. Metabolic abnormalities are commonly observed in patients with Alzheimer's disease. The liver is the primary peripheral organ involved in amyloid-beta metabolism, playing a crucial role in the pathophysiology of Alzheimer's disease. Notably, impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease. In this review, we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism. Furthermore, we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11433892PMC
http://dx.doi.org/10.4103/1673-5374.391305DOI Listing

Publication Analysis

Top Keywords

alzheimer's disease
36
cholesterol metabolism
16
amyloid-beta clearance
12
alzheimer's
9
disease
9
amyloid plaques
8
central nervous
8
nervous system
8
metabolism liver
8
liver
5

Similar Publications

Background: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear.

Method: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform.

View Article and Find Full Text PDF

Polygenic genome editing in human embryos and germ cells is predicted to become feasible in the next three decades. Several recent books and academic papers have outlined the ethical concerns raised by germline genome editing and the opportunities that it may present. To date, no attempts have been made to predict the consequences of altering specific variants associated with polygenic diseases.

View Article and Find Full Text PDF

Stereo-seq of the prefrontal cortex in aging and Alzheimer's disease.

Nat Commun

January 2025

Tulane Center for Biomedical Informatics and Genomics, Deming Department of Medicine, School of Medicine, Tulane University, New Orleans, LA, 70112, USA.

Aging increases the risk for Alzheimer's disease (AD), driving pathological changes like amyloid-β (Aβ) buildup, inflammation, and oxidative stress, especially in the prefrontal cortex (PFC). We present the first subcellular-resolution spatial transcriptome atlas of the human prefrontal cortex (PFC), generated with Stereo-seq from six male AD cases at varying neuropathological stages and six age-matched male controls. Our analyses revealed distinct transcriptional alterations across PFC layers, highlighted disruptions in laminar structure, and exposed AD-related shifts in layer-to-layer and cell-cell interactions.

View Article and Find Full Text PDF

Objective: To summarise available evidence on time to nursing home admission and death among people with dementia, and to explore prognostic indicators.

Design: Systematic review and meta-analysis.

Data Sources: Medline, Embase, Web of Science, Cochrane, and Google Scholar from inception to 4 July 2024.

View Article and Find Full Text PDF

The Alzheimer's Association and the Society of Nuclear Medicine and Molecular Imaging convened a multidisciplinary workgroup to update appropriate use criteria (AUC) for amyloid positron emission tomography (PET) and to develop AUC for tau PET. The workgroup identified key research questions that guided a systematic literature review on clinical amyloid/tau PET. Building on this review, the workgroup developed 17 clinical scenarios in which amyloid or tau PET may be considered.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!