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

Abstract

AimsThe study attempted to determine the underlying role and regulation mechanism of 3β‐hydroxysterol‐Δ24 reductase (DHCR24) in the pathophysiology of cerebral small vessel disease‐associated cognitive impairment (CSVD‐CI). An RNA high‐throughput sequencing and independent verification were conducted to identify potential circRNAs becoming the upstream regulator.MethodsRNA sequencing was performed in whole‐blood samples in cohort 1 (10 CSVD‐CI and 8 CSVD with cognitively normal [CSVD‐CN] patients). The DHCR24 and candidate circRNAs were verified in an independent cohort 2 (45 CSVD‐CI participants and 37 CSVD‐CN ones). The study also analyzed comprehensive cognitive assessments, plasma molecular index, and brain structure imaging.ResultsThe expression of DHCR24 and has_circ_0015335 in whole‐blood samples of CSVD‐CI patients was significantly reduced compared to CSVD‐CN patients in RNA sequencing and independent verification. Furthermore, the levels of DHCR24 and has_circ_0015335 were significantly related to global cognitive impairment in CSVD‐CI patients. Meanwhile, DHCR24 could regulate the correlation between has_circ_0015335 expression and alterations in brain cortex in surface area, thickness, and volume in CSVD‐CI patients. Additionally, hsa_circ_0015335 interacted with DHCR24 for plasma 24(S)‐hydroxycholesterol levels among CSVD‐CI patients.ConclusionInteraction between DHCR24 and hsa_circ_0015335 cognitively impaired CSVD by affecting brain cholesterol metabolism and brain structural changes.