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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. © 2019 International Parkinson and Movement Disorder Society.

SUBMITTER: Huang X

PROVIDER: S-EPMC6420391 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Brain cholesterol metabolism and Parkinson's disease.

Huang Xuemei X Sterling Nicholas W NW Du Guangwei G Sun Dongxiao D Stetter Christina C Kong Lan L Zhu Yusheng Y Neighbors Jeffery J Lewis Mechelle M MM Chen Honglei H Hohl Raymond J RJ Mailman Richard B RB

Movement disorders : official journal of the Movement Disorder Society 20190125 3

<h4>Background</h4>Circulating cholesterol levels have been linked to PD, but not directly to brain physiology.<h4>Objective</h4>To assess whether brain cholesterol metabolism is related to PD.<h4>Methods</h4>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 (periphera ...[more]

PMID: 30681742

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Project description:RationaleIn Parkinson's disease (PD), spatial covariance analysis of 18F-FDG PET data has consistently revealed a characteristic PD-related brain pattern (PDRP). By quantifying PDRP expression on a scan-by-scan basis, this technique allows objective assessment of disease activity in individual subjects. We provide a further validation of the PDRP by applying spatial covariance analysis to PD cohorts from the Netherlands (NL), Italy (IT), and Spain (SP).MethodsThe PDRPNL was previously identified (17 controls, 19 PD) and its expression was determined in 19 healthy controls and 20 PD patients from the Netherlands. The PDRPIT was identified in 20 controls and 20 "de-novo" PD patients from an Italian cohort. A further 24 controls and 18 "de-novo" Italian patients were used for validation. The PDRPSP was identified in 19 controls and 19 PD patients from a Spanish cohort with late-stage PD. Thirty Spanish PD patients were used for validation. Patterns of the three centers were visually compared and then cross-validated. Furthermore, PDRP expression was determined in 8 patients with multiple system atrophy.ResultsA PDRP could be identified in each cohort. Each PDRP was characterized by relative hypermetabolism in the thalamus, putamen/pallidum, pons, cerebellum, and motor cortex. These changes co-varied with variable degrees of hypometabolism in posterior parietal, occipital, and frontal cortices. Frontal hypometabolism was less pronounced in "de-novo" PD subjects (Italian cohort). Occipital hypometabolism was more pronounced in late-stage PD subjects (Spanish cohort). PDRPIT, PDRPNL, and PDRPSP were significantly expressed in PD patients compared with controls in validation cohorts from the same center (P < 0.0001), and maintained significance on cross-validation (P < 0.005). PDRP expression was absent in MSA.ConclusionThe PDRP is a reproducible disease characteristic across PD populations and scanning platforms globally. Further study is needed to identify the topography of specific PD subtypes, and to identify and correct for center-specific effects.

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Brain cholesterol metabolism and Parkinson's disease.

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Brain cholesterol metabolism and Parkinson's disease.

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