Abstract

Background: Circulating cholesterol levels have been linked to PD, but not directly to brain physiology. Objective: To assess whether brain cholesterol metabolism is related to PD. Methods: Sixty PD patients and 64 controls were recruited from an academic movement disorder clinic (2009–2012). Thirty-five PD patients and 33 controls returned approximately 36 months later. Fasting plasma (S)24-OH-cholesterol (brain-derived cholesterol metabolite) and 27-OH-cholesterol (peripheral cholesterol metabolite) were quantified. Odds ratios for PD were derived from logistic regression models, adjusting for potential confounders. Relationships between the oxysterols and clinical measurements were explored using Spearman correlation coefficients. Results: Mean age of PD subjects was 63.8 ± 8.3 years and disease duration was 5.0 ± 5.4 years. Plasma (S)24-OH-cholesterol levels were inversely associated with the odds of having PD, with an odds ratio of 0.92 (95% confidence interval: 0.87–0.97) for each 1-ng/mL increase (P = 0.004). Compared to the lowest tertile, the odds ratio was 0.34 (0.12–0.98) for the second tertile (P = 0.045) and 0.08 (0.02–0.31) for the highest tertile (P < 0.001). Higher (S)24-OH-cholesterol levels also were correlated with better sense of smell (r = 0.35; P = 0.01). No significant associations were found between clinical measures and 27-OH-cholesterol, a peripheral cholesterol metabolite. Furthermore, (S)24-OH-cholesterol levels were stable over time, whereas 27-OH-cholesterol decreased with time in both cases and controls. Conclusions: Results indicate that plasma (S)24-OH-cholesterol (possibly reflecting brain cholesterol metabolism) is inversely linked to PD, is relatively stable over time, and may serve as a new biomarker for PD. Further investigation is necessary to determine the mechanistic and clinical implications.

Original languageEnglish (US)
Pages (from-to)386-395
Number of pages10
JournalMovement Disorders
Volume34
Issue number3
DOIs
StatePublished - Mar 1 2019

Fingerprint

Parkinson Disease
Cholesterol
Brain
Odds Ratio
Logistic Models
hydroxide ion
Smell
Movement Disorders
Fasting
Biomarkers
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

@article{15f7ee3a260544e28bee21364120c10d,
title = "Brain cholesterol metabolism and Parkinson's disease",
abstract = "Background: Circulating cholesterol levels have been linked to PD, but not directly to brain physiology. Objective: To assess whether brain cholesterol metabolism is related to PD. Methods: Sixty PD patients and 64 controls were recruited from an academic movement disorder clinic (2009–2012). Thirty-five PD patients and 33 controls returned approximately 36 months later. Fasting plasma (S)24-OH-cholesterol (brain-derived cholesterol metabolite) and 27-OH-cholesterol (peripheral cholesterol metabolite) were quantified. Odds ratios for PD were derived from logistic regression models, adjusting for potential confounders. Relationships between the oxysterols and clinical measurements were explored using Spearman correlation coefficients. Results: Mean age of PD subjects was 63.8 ± 8.3 years and disease duration was 5.0 ± 5.4 years. Plasma (S)24-OH-cholesterol levels were inversely associated with the odds of having PD, with an odds ratio of 0.92 (95{\%} confidence interval: 0.87–0.97) for each 1-ng/mL increase (P = 0.004). Compared to the lowest tertile, the odds ratio was 0.34 (0.12–0.98) for the second tertile (P = 0.045) and 0.08 (0.02–0.31) for the highest tertile (P < 0.001). Higher (S)24-OH-cholesterol levels also were correlated with better sense of smell (r = 0.35; P = 0.01). No significant associations were found between clinical measures and 27-OH-cholesterol, a peripheral cholesterol metabolite. Furthermore, (S)24-OH-cholesterol levels were stable over time, whereas 27-OH-cholesterol decreased with time in both cases and controls. Conclusions: Results indicate that plasma (S)24-OH-cholesterol (possibly reflecting brain cholesterol metabolism) is inversely linked to PD, is relatively stable over time, and may serve as a new biomarker for PD. Further investigation is necessary to determine the mechanistic and clinical implications.",
author = "Xuemei Huang and Sterling, {Nicholas W.} and Guangwei Du and Dongxiao Sun and Christina Stetter and Lan Kong and Yusheng Zhu and Jeffrey Neighbors and Mechelle Lewis and Honglei Chen and Raymond Hohl and Richard Mailman",
year = "2019",
month = "3",
day = "1",
doi = "10.1002/mds.27609",
language = "English (US)",
volume = "34",
pages = "386--395",
journal = "Movement Disorders",
issn = "0885-3185",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

Brain cholesterol metabolism and Parkinson's disease. / Huang, Xuemei; Sterling, Nicholas W.; Du, Guangwei; Sun, Dongxiao; Stetter, Christina; Kong, Lan; Zhu, Yusheng; Neighbors, Jeffrey; Lewis, Mechelle; Chen, Honglei; Hohl, Raymond; Mailman, Richard.

In: Movement Disorders, Vol. 34, No. 3, 01.03.2019, p. 386-395.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Brain cholesterol metabolism and Parkinson's disease

AU - Huang, Xuemei

AU - Sterling, Nicholas W.

AU - Du, Guangwei

AU - Sun, Dongxiao

AU - Stetter, Christina

AU - Kong, Lan

AU - Zhu, Yusheng

AU - Neighbors, Jeffrey

AU - Lewis, Mechelle

AU - Chen, Honglei

AU - Hohl, Raymond

AU - Mailman, Richard

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Background: Circulating cholesterol levels have been linked to PD, but not directly to brain physiology. Objective: To assess whether brain cholesterol metabolism is related to PD. Methods: Sixty PD patients and 64 controls were recruited from an academic movement disorder clinic (2009–2012). Thirty-five PD patients and 33 controls returned approximately 36 months later. Fasting plasma (S)24-OH-cholesterol (brain-derived cholesterol metabolite) and 27-OH-cholesterol (peripheral cholesterol metabolite) were quantified. Odds ratios for PD were derived from logistic regression models, adjusting for potential confounders. Relationships between the oxysterols and clinical measurements were explored using Spearman correlation coefficients. Results: Mean age of PD subjects was 63.8 ± 8.3 years and disease duration was 5.0 ± 5.4 years. Plasma (S)24-OH-cholesterol levels were inversely associated with the odds of having PD, with an odds ratio of 0.92 (95% confidence interval: 0.87–0.97) for each 1-ng/mL increase (P = 0.004). Compared to the lowest tertile, the odds ratio was 0.34 (0.12–0.98) for the second tertile (P = 0.045) and 0.08 (0.02–0.31) for the highest tertile (P < 0.001). Higher (S)24-OH-cholesterol levels also were correlated with better sense of smell (r = 0.35; P = 0.01). No significant associations were found between clinical measures and 27-OH-cholesterol, a peripheral cholesterol metabolite. Furthermore, (S)24-OH-cholesterol levels were stable over time, whereas 27-OH-cholesterol decreased with time in both cases and controls. Conclusions: Results indicate that plasma (S)24-OH-cholesterol (possibly reflecting brain cholesterol metabolism) is inversely linked to PD, is relatively stable over time, and may serve as a new biomarker for PD. Further investigation is necessary to determine the mechanistic and clinical implications.

AB - Background: Circulating cholesterol levels have been linked to PD, but not directly to brain physiology. Objective: To assess whether brain cholesterol metabolism is related to PD. Methods: Sixty PD patients and 64 controls were recruited from an academic movement disorder clinic (2009–2012). Thirty-five PD patients and 33 controls returned approximately 36 months later. Fasting plasma (S)24-OH-cholesterol (brain-derived cholesterol metabolite) and 27-OH-cholesterol (peripheral cholesterol metabolite) were quantified. Odds ratios for PD were derived from logistic regression models, adjusting for potential confounders. Relationships between the oxysterols and clinical measurements were explored using Spearman correlation coefficients. Results: Mean age of PD subjects was 63.8 ± 8.3 years and disease duration was 5.0 ± 5.4 years. Plasma (S)24-OH-cholesterol levels were inversely associated with the odds of having PD, with an odds ratio of 0.92 (95% confidence interval: 0.87–0.97) for each 1-ng/mL increase (P = 0.004). Compared to the lowest tertile, the odds ratio was 0.34 (0.12–0.98) for the second tertile (P = 0.045) and 0.08 (0.02–0.31) for the highest tertile (P < 0.001). Higher (S)24-OH-cholesterol levels also were correlated with better sense of smell (r = 0.35; P = 0.01). No significant associations were found between clinical measures and 27-OH-cholesterol, a peripheral cholesterol metabolite. Furthermore, (S)24-OH-cholesterol levels were stable over time, whereas 27-OH-cholesterol decreased with time in both cases and controls. Conclusions: Results indicate that plasma (S)24-OH-cholesterol (possibly reflecting brain cholesterol metabolism) is inversely linked to PD, is relatively stable over time, and may serve as a new biomarker for PD. Further investigation is necessary to determine the mechanistic and clinical implications.

UR - http://www.scopus.com/inward/record.url?scp=85060615805&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060615805&partnerID=8YFLogxK

U2 - 10.1002/mds.27609

DO - 10.1002/mds.27609

M3 - Article

C2 - 30681742

AN - SCOPUS:85060615805

VL - 34

SP - 386

EP - 395

JO - Movement Disorders

JF - Movement Disorders

SN - 0885-3185

IS - 3

ER -