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Interaction Between DHCR24 and hsa_circ_0015335 Facilitates Cognitive Impairment in Cerebral Small Vessel Disease

Yachen Shi1,2, Min Xu3, Feng Wang1,2

  • 1Department of Neurology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China.

CNS Neuroscience & Therapeutics
|November 23, 2024
PubMed

Insights

Reduced expression of DHCR24 and has_circ_0015335 is linked to cognitive impairment in cerebral small vessel disease (CSVD-CI). These factors interact, affecting cholesterol metabolism and brain structure in CSVD-CI patients.

Area of Science:

  • Neuroscience
  • Genetics
  • Biochemistry

Background:

  • Cerebral small vessel disease-associated cognitive impairment (CSVD-CI) poses a significant neurological challenge.
  • The role of 3β-hydroxysterol-Δ24 reductase (DHCR24) in CSVD-CI pathophysiology remains incompletely understood.
  • Identifying upstream regulators like circRNAs is crucial for understanding CSVD-CI mechanisms.

Purpose of the Study:

  • To elucidate the role and regulatory mechanism of DHCR24 in CSVD-CI.
  • To identify potential upstream regulatory circRNAs involved in CSVD-CI.
  • To investigate the relationship between DHCR24, circRNAs, and cognitive impairment in CSVD-CI.

Main Methods:

  • RNA high-throughput sequencing and independent verification of gene and circRNA expression in whole-blood samples.
  • Analysis of two cohorts: Cohort 1 (10 CSVD-CI, 8 CSVD-CN) and Cohort 2 (45 CSVD-CI, 37 CSVD-CN).
  • Comprehensive cognitive assessments, plasma molecular index analysis, and brain structure imaging.

Main Results:

  • Significantly reduced expression of DHCR24 and has_circ_0015335 in CSVD-CI patients compared to controls.
  • DHCR24 and has_circ_0015335 levels correlated with global cognitive impairment in CSVD-CI.
  • DHCR24 regulated the association between has_circ_0015335 expression and brain structural alterations (surface area, thickness, volume).
  • hsa_circ_0015335 interacted with DHCR24 to influence plasma 24(S)-hydroxycholesterol levels in CSVD-CI patients.

Conclusions:

  • DHCR24 and has_circ_0015335 play a significant role in CSVD-CI pathophysiology.
  • Their interaction impacts brain cholesterol metabolism and structural changes, contributing to cognitive impairment.
  • These findings highlight potential therapeutic targets for CSVD-CI.
Abstract

Keywords:
brain magnetic resonance imagingcerebral small vessel diseasecholesterol metabolismcircRNAcognitive impairmentmRNA

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