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Cholesterol profiling reveals 7β‐hydroxycholesterol as a pathologically relevant peripheral biomarker of Alzheimer's disease.

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Title: Cholesterol profiling reveals 7β‐hydroxycholesterol as a pathologically relevant peripheral biomarker of Alzheimer's disease.
Authors: Ha, Junghee (AUTHOR), Kwon, Go Eun (AUTHOR), Son, Yumi (AUTHOR), Jang, Soo Ah (AUTHOR), Cho, So Yeon (AUTHOR), Park, Soo Jin (AUTHOR), Kim, Hyunjeong (AUTHOR), Lee, Jimin (AUTHOR), Lee, Juseok (AUTHOR), Seo, Dongryul (AUTHOR), Lee, Myeongjee (AUTHOR), Lee, Do Yup (AUTHOR), Choi, Man Ho (AUTHOR), Kim, Eosu (AUTHOR)
Source: Psychiatry & Clinical Neurosciences. Aug2024, Vol. 78 Issue 8, p473-481. 9p.
Subjects: Executive function, Recognition (Psychology), Alzheimer's disease, Mild cognitive impairment, Individualized medicine, Compulsive hair pulling
Abstract: Aim: Cholesterol 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. Methods: To 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. Results: The 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. Conclusions: Our 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. [ABSTRACT FROM AUTHOR]
Copyright of Psychiatry & Clinical Neurosciences is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Cholesterol profiling reveals 7β‐hydroxycholesterol as a pathologically relevant peripheral biomarker of Alzheimer's disease.
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  Data: <searchLink fieldCode="AR" term="%22Ha%2C+Junghee%22">Ha, Junghee</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kwon%2C+Go+Eun%22">Kwon, Go Eun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Son%2C+Yumi%22">Son, Yumi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Jang%2C+Soo+Ah%22">Jang, Soo Ah</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cho%2C+So+Yeon%22">Cho, So Yeon</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Park%2C+Soo+Jin%22">Park, Soo Jin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kim%2C+Hyunjeong%22">Kim, Hyunjeong</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lee%2C+Jimin%22">Lee, Jimin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lee%2C+Juseok%22">Lee, Juseok</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Seo%2C+Dongryul%22">Seo, Dongryul</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lee%2C+Myeongjee%22">Lee, Myeongjee</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lee%2C+Do+Yup%22">Lee, Do Yup</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Choi%2C+Man+Ho%22">Choi, Man Ho</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kim%2C+Eosu%22">Kim, Eosu</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Psychiatry+%26+Clinical+Neurosciences%22">Psychiatry & Clinical Neurosciences</searchLink>. Aug2024, Vol. 78 Issue 8, p473-481. 9p.
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  Label: Subjects
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  Data: <searchLink fieldCode="DE" term="%22Executive+function%22">Executive function</searchLink><br /><searchLink fieldCode="DE" term="%22Recognition+%28Psychology%29%22">Recognition (Psychology)</searchLink><br /><searchLink fieldCode="DE" term="%22Alzheimer's+disease%22">Alzheimer's disease</searchLink><br /><searchLink fieldCode="DE" term="%22Mild+cognitive+impairment%22">Mild cognitive impairment</searchLink><br /><searchLink fieldCode="DE" term="%22Individualized+medicine%22">Individualized medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Compulsive+hair+pulling%22">Compulsive hair pulling</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Aim: Cholesterol 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. Methods: To 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. Results: The 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. Conclusions: Our 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. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of Psychiatry & Clinical Neurosciences is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1111/pcn.13706
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        Text: English
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        PageCount: 9
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      – SubjectFull: Executive function
        Type: general
      – SubjectFull: Recognition (Psychology)
        Type: general
      – SubjectFull: Alzheimer's disease
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      – SubjectFull: Mild cognitive impairment
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              Text: Aug2024
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