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.
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http://dx.doi.org/10.4103/1673-5374.391305 | DOI Listing |
Commun Med (Lond)
January 2025
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA.
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.
Nature
January 2025
Murdoch Children's Research Institute, Melbourne, Victoria, Australia.
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 PDFNat 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 PDFBMJ
January 2025
Department of Epidemiology, Erasmus MC University Medical Centre, Rotterdam, Netherlands
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.
J Nucl Med
January 2025
Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts.
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.
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