ArticlePsychiatry and clinical neurosciences2024
Cholesterol profiling reveals 7β-hydroxycholesterol as a pathologically relevant peripheral biomarker of Alzheimer's disease.
Article in Psychiatry and clinical neurosciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Lipidomic and sterolomic profiles of different brain regions in the mouse model of Alzheimer's disease.Neural regeneration research · 2026Article
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Longitudinal Evaluation of the Detection Potential of Serum Oligoelements Cu, Se and Zn for the Diagnosis of Alzheimer's Disease in the 3xTg-AD Animal Model.International journal of molecular sciences · 2025Article
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14 authors.
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Abstract
aimCholesterol homeostasis is associated with Alzheimer's disease (AD). Despite the multitude of cholesterol metabolites, little is known about which metabolites are directly involved in AD pathogenesis and can serve as its potential biomarkers.
methodsTo identify "hit" metabolites, steroid profiling was conducted in mice with different age, diet, and genotype and also in humans with normal cognition, mild cognitive impairment, and AD using gas chromatography-mass spectrometry. Then, using one of the "hit" molecules (7β-hydroxycholesterol; OHC), molecular and histopathological experiment and behavioral testing were conducted in normal mice following its intracranial stereotaxic injection to see whether this molecule drives AD pathogenesis and causes cognitive impairment.
resultsThe serum levels of several metabolites, including 7β-OHC, were increased by aging in the 3xTg-AD unlike normal mice. Consistently, the levels of 7β-OHC were increased in the hairs of patients with AD and were correlated with clinical severity. We found that 7β-OHC directly affects AD-related pathophysiology; intrahippocampal injection of 7β-OHC induced astrocyte and microglial cell activation, increased the levels of pro-inflammatory cytokines (TNF-alpha, IL-1β, IL-6), and enhanced amyloidogenic pathway. Mice treated with 7β-OHC also exhibited deficits in memory and frontal/executive functions assessed by object recognition and 5-choice serial reaction time task, respectively.
conclusionsOur results suggest that 7β-OHC could serve as a convenient, peripheral biomarker of AD. As directly involved in AD pathogenesis, 7β-OHC assay may help actualize personalized medicine in a way to identify an at-risk subgroup as a candidate population for statin-based AD treatment.
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