Molecular markers of brain cholesterol homeostasis are unchanged despite a smaller brain mass in a mouse model of cholesteryl ester storage disease

Lipids ◽  
2021 ◽  
Author(s):  
Amal A. Aqul ◽  
Charina M. Ramirez ◽  
Adam M. Lopez ◽  
Dennis K. Burns ◽  
Joyce J. Repa ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Mouse Model ◽  
Cholesteryl Ester ◽  
Storage Disease ◽  
Cholesterol Homeostasis ◽  
Brain Mass ◽  
Brain Cholesterol

scholarly journals Abnormal brain cholesterol homeostasis in Alzheimer’s disease—a targeted metabolomic and transcriptomic study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Vijay R. Varma ◽  
H. Büşra Lüleci ◽  
Anup M. Oommen ◽  
Sudhir Varma ◽  
Chad T. Blackshear ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Tissue ◽  
Cholesterol Metabolism ◽  
Cholesterol Biosynthesis ◽  
Cholesterol Homeostasis ◽  
Transcriptomic Data ◽  
Brain Cholesterol ◽  
Cholesterol Levels

AbstractThe role of brain cholesterol metabolism in Alzheimer’s disease (AD) remains unclear. Peripheral and brain cholesterol levels are largely independent due to the impermeability of the blood brain barrier (BBB), highlighting the importance of studying the role of brain cholesterol homeostasis in AD. We first tested whether metabolite markers of brain cholesterol biosynthesis and catabolism were altered in AD and associated with AD pathology using linear mixed-effects models in two brain autopsy samples from the Baltimore Longitudinal Study of Aging (BLSA) and the Religious Orders Study (ROS). We next tested whether genetic regulators of brain cholesterol biosynthesis and catabolism were altered in AD using the ANOVA test in publicly available brain tissue transcriptomic datasets. Finally, using regional brain transcriptomic data, we performed genome-scale metabolic network modeling to assess alterations in cholesterol biosynthesis and catabolism reactions in AD. We show that AD is associated with pervasive abnormalities in cholesterol biosynthesis and catabolism. Using transcriptomic data from Parkinson’s disease (PD) brain tissue samples, we found that gene expression alterations identified in AD were not observed in PD, suggesting that these changes may be specific to AD. Our results suggest that reduced de novo cholesterol biosynthesis may occur in response to impaired enzymatic cholesterol catabolism and efflux to maintain brain cholesterol levels in AD. This is accompanied by the accumulation of nonenzymatically generated cytotoxic oxysterols. Our results set the stage for experimental studies to address whether abnormalities in cholesterol metabolism are plausible therapeutic targets in AD.

scholarly journals Compound heterozygosity for a Wolman mutation is frequent among patients with cholesteryl ester storage disease

2000 ◽  
Vol 41 (1) ◽  
pp. 23-31
Author(s):  
Peter Lohse ◽  
Sylke Maas ◽  
Pia Lohse ◽  
Milan Elleder ◽  
Jean M. Kirk ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Storage Disease ◽  
Compound Heterozygosity

scholarly journals Monitoring the correction of glycogen storage disease type 1a in a mouse model using [18F]FDG and a dedicated animal scanner

Life Sciences ◽  
2002 ◽  
Vol 71 (11) ◽  
pp. 1293-1301 ◽  
Author(s):  
A. Zingone ◽  
J. Seidel ◽  
L. Aloj ◽  
C. Caraco ◽  
J.J. Vaquero ◽  
...  
Keyword(s):  
Mouse Model ◽  
Glycogen Storage Disease ◽  
Storage Disease ◽  
Glycogen Storage Disease Type ◽  
Glycogen Storage ◽  
Disease Type ◽  
18F Fdg
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