ArticleNPJ aging and mechanisms of disease2021
Abnormal brain cholesterol homeostasis in Alzheimer's disease-a targeted metabolomic and transcriptomic study.
Article in NPJ aging and mechanisms of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 140 citations in OpenAlex.
- CYP46A1 activation by low-dose efavirenz enhances brain cholesterol metabolism in subjects with early Alzheimer's disease.Alzheimer's research & therapy · 2022Trial
- Cholesterol maintains the degradative capacity of lysosomes during clearance and recycling of dysfunctional mitochondria.Nature communications · 2026Article
- Molecular programs in human locus coeruleus link APOE and neuromelanin to Alzheimer's vulnerability.Acta neuropathologica · 2026Article
- Bile acids in Alzheimer's disease: a double-edged sword in gut-liver-brain signaling and neurodegeneration.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Unique transcriptomic alterations in 5XFAD;PS19 mouse model identify glial lipid dysregulation and coordinated microglial-oligodendrocyte responses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Nobiletin Modulates Transcriptomic and Metabolomic Alterations in Aβ42-Induced Primary Rat Astrocytes: Implications for Alzheimer's Disease.Molecular neurobiology · 2026Article
- Quantitative determination of longitudinal CNS cholesterol loss during myelin damage and repair.bioRxiv : the preprint server for biology · 2026Article
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Microglial cholesterol reprogramming drives cognitive impairment under hypobaric hypoxia.Journal of neuroinflammation · 2026Article
- Personalized metabolite biomarker predictions reveal heterogeneous characteristics of Parkinson's disease.NPJ Parkinson's disease · 2026Article
- DHCR24 in cholesterol metabolism and diseases of the nervous system.Lipids in health and disease · 2026Review
- Chicoric acid enhanced brain cholesterol efflux and reduced Aβ pathology via LXR-ABCA1 signaling in Alzheimer's models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Article
- Metabolic Dysregulation of 27-Hydroxycholesterol Sensitizes Proximal Tubular Epithelial Cells to Ferroptosis in Ischemic Acute Kidney Injury.Journal of the American Society of Nephrology : JASN · 2026Article
- Cell-specific effects of acute sleep deprivation on transcriptomic signatures of non-neuronal cells in the mouse hippocampus and prefrontal cortex.bioRxiv : the preprint server for biology · 2026Article
- The heterogeneous treatment effects of statins on dementia: a target trial emulation with causal machine learning using integrated genetic and real-world data.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Mechanisms, Mediators, and Pharmacological Approaches Targeting Brain Cholesterol Transport in Alzheimer's Disease.Current pharmaceutical design · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Relationships between heritable dementia risk factors, cardiovascular risk factors in young adulthood, and midlife neuropsychological outcomes.Journal of Alzheimer's disease : JAD · 2026Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 4 countries.
Funding
Abstract
The role of brain cholesterol metabolism in Alzheimer's disease (AD) remains unclear. Peripheral and brain cholesterol levels are largely independent due to the impermeability of the blood brain barrier (BBB), highlighting the importance of studying the role of brain cholesterol homeostasis in AD. We first tested whether metabolite markers of brain cholesterol biosynthesis and catabolism were altered in AD and associated with AD pathology using linear mixed-effects models in two brain autopsy samples from the Baltimore Longitudinal Study of Aging (BLSA) and the Religious Orders Study (ROS). We next tested whether genetic regulators of brain cholesterol biosynthesis and catabolism were altered in AD using the ANOVA test in publicly available brain tissue transcriptomic datasets. Finally, using regional brain transcriptomic data, we performed genome-scale metabolic network modeling to assess alterations in cholesterol biosynthesis and catabolism reactions in AD. We show that AD is associated with pervasive abnormalities in cholesterol biosynthesis and catabolism. Using transcriptomic data from Parkinson's disease (PD) brain tissue samples, we found that gene expression alterations identified in AD were not observed in PD, suggesting that these changes may be specific to AD. Our results suggest that reduced de novo cholesterol biosynthesis may occur in response to impaired enzymatic cholesterol catabolism and efflux to maintain brain cholesterol levels in AD. This is accompanied by the accumulation of nonenzymatically generated cytotoxic oxysterols. Our results set the stage for experimental studies to address whether abnormalities in cholesterol metabolism are plausible therapeutic targets in AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.