Dataset Information

Alterations in the Plasma Levels of Specific Choline Phospholipids in Alzheimer's Disease Mimic Accelerated Aging.

ABSTRACT: Alzheimer's disease (AD) is the most common neurodegenerative disease and of continuously rising prevalence. The identification of easy-to-measure biomarkers capable to assist in the prediction and early diagnosis of AD is currently a main research goal. Lipid metabolites in peripheral blood of human patients have recently gained major attention in this respect. Here, we analyzed plasma of 174 participants (not demented at baseline; mean age: 75.70±0.44 years) of the Vienna Transdanube Aging (VITA) study, a longitudinal, population-based birth cohort study, at baseline and after 90 months or at diagnosis of probable AD. We determined the levels of specific choline phospholipids, some of which have been suggested as potential biomarkers for the prediction of AD. Our results show that during normal aging the levels of lysophosphatidylcholine, choline plasmalogen, and lyso-platelet activating factor increase significantly. Notably, we observed similar but more pronounced changes in the group that developed probable AD. Thus, our results imply that, in terms of choline-containing plasma phospholipids, the conversion to AD mimics an accelerated aging process. We conclude that age, even in the comparatively short time frame between 75 and 82.5 years, is a crucial factor in the quest for plasma lipid biomarkers for AD that must be carefully considered in future studies and trials.

SUBMITTER: Dorninger F

PROVIDER: S-EPMC5837024 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Alterations in the Plasma Levels of Specific Choline Phospholipids in Alzheimer's Disease Mimic Accelerated Aging.

Dorninger Fabian F Moser Ann B AB Kou Jianqiu J Wiesinger Christoph C Forss-Petter Sonja S Gleiss Andreas A Hinterberger Margareta M Jungwirth Susanne S Fischer Peter P Berger Johannes J

Journal of Alzheimer's disease : JAD 20180101 2

Alzheimer's disease (AD) is the most common neurodegenerative disease and of continuously rising prevalence. The identification of easy-to-measure biomarkers capable to assist in the prediction and early diagnosis of AD is currently a main research goal. Lipid metabolites in peripheral blood of human patients have recently gained major attention in this respect. Here, we analyzed plasma of 174 participants (not demented at baseline; mean age: 75.70±0.44 years) of the Vienna Transdanube Aging (VI ...[more]

PMID: 29480199

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Project description:Alzheimer's disease (AD) is the most common cause of dementia with no effective therapies. Aging is a dominant risk factor for AD. The neurovascular unit (NVU) plays an important role in maintaining homeostasis of the brain microenvironment. The accelerated aging of NVU cells may directly impair NVU function and contribute to AD pathogenesis. However, the expression patterns of aging-related genes (AGs) in NVU cells of AD remain unclear. In this study, we performed single-nucleus transcriptome analysis of 61,768 nuclei from prefrontal cortical samples of patients with AD and normal control (NC) subjects. Eight main cell types were identified, including astrocytes, microglia, excitatory neurons, inhibitory neurons, oligodendrocytes, oligodendrocyte precursor cells, pericytes, and endothelial cells. Transcriptomic analysis identified the expression patterns of AGs in NVU cells of AD. Gene set enrichment analysis confirmed the key aging-associated cellular pathways enriched in microglia and oligodendrocytes. These aging-related transcriptomic changes in NVU were cross-validated using bulk transcriptome data. The least absolute shrinkage and selection operator regression method was used to select the crucial AGs most associated with AD: IGF1R, MXI1, RB1, PPARA, NFE2L2, STAT5B, FOS, PRKCD, YWHAZ, HTT, MAPK9, HSPA9, SDHC, PRKDC, and PDPK1. This 15-gene model performed well in discriminating AD from NC samples. Among them, IGF1R, MXI1, PPARA, YWHAZ, and MAPK9 strongly correlated with pathologic progression in AD, were identified as critical regulators of AD. Although most AGs showed similar trends of expression changes in different types of NVU cells in AD, certain AGs were expressed in a cell-specific manner. Our comprehensive analysis of brain NVU from patients with AD reveals previously unknown molecular changes associated with aging that may underlie the functional dysregulation of NVU, providing important insights for exploring potential cell-specific therapeutic targets to restore brain homeostasis in AD.

Project description:Sleepiness and cardiovascular disease share common molecular pathways; thus, metabolic risk factors for sleepiness may also predict cardiovascular disease risk. Daytime sleepiness predicts mortality and cardiovascular disease, although the mechanism is unidentified. This study explored the associations between subjective sleepiness and metabolite concentrations in human blood plasma within the oxidative and inflammatory pathways, in order to identify mechanisms that may contribute to sleepiness and cardiovascular disease risk.MethodsAn exploratory case-control sample of 36 subjects, categorized based on the Epworth Sleepiness Scale (ESS) questionnaire as sleepy (ESS ≥ 10) or non-sleepy (ESS < 10), was recruited among subjects undergoing an overnight sleep study for suspected sleep apnea at the University of Pennsylvania Sleep Center. The average age was 42.4 ± 10.5 years, the mean body mass index (BMI) was 40.0 ± 9.36 kg/m2, median Apnea Hypopnea Index (AHI) was 8.2 (IQR: 2.5-26.5), and 52% were male. Fasting morning blood plasma samples were collected after an overnight sleep study. Biomarkers were explored in subjects with sleepiness versus those without using the multiple linear regression adjusting for age, BMI, smoking, Apnea Hypopnea Index (sleep apnea severity), study cohort, and hypertension.ResultsThe level of choline is significantly lower (P = 0.003) in sleepy subjects (N = 18; mean plasma choline concentration of 8.19 ± 2.62 μmol/L) compared with non-sleepy subjects (N = 18; mean plasma choline concentration of 9.14 ± 2.25 μmol/L). Other markers with suggestive differences (P < 0.1) include isovalerylcarnitine, Alpha-Amino apidipic acid, Spingosine 1 Phosphate, Aspartic Acid, Propionylcarnitine, and Ceramides (fatty acids; C14-C16 and C-18).ConclusionThis pilot study is the first to show that lower levels of plasma choline metabolites are associated with sleepiness. Further exploration of choline and other noted metabolites and their associations with sleepiness will guide targeted symptom management.

Dataset Information

Alterations in the Plasma Levels of Specific Choline Phospholipids in Alzheimer's Disease Mimic Accelerated Aging.

Publications

Alterations in the Plasma Levels of Specific Choline Phospholipids in Alzheimer's Disease Mimic Accelerated Aging.

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