Bile acid synthesis, modulation, and dementia: A metabolomic, transcriptomic, and pharmacoepidemiologic study.
Vijay R VarmaYoujin WangYang AnSudhir VarmaMurat BilgelJimit DoshiCristina Legido-QuigleyJoão C DelgadoAnup M OommenJackson A RobertsDean F WongChristos DavatzikosSusan M ResnickJuan C TroncosoOlga PletnikovaRichard O'BrienEelko HakBrenda N BaakRuth PfeifferPriyanka BaloniSiamak MahmoudiandehkordiKwangsik T NhoRima Kaddurah-DaoukDavid A BennettShahinaz M GadallaMadhav ThambisettyPublished in: PLoS medicine (2021)
We combined targeted metabolomics in serum and amyloid positron emission tomography (PET) and MRI of the brain with pharmacoepidemiologic analysis to implicate dysregulation of cholesterol catabolism in dementia pathogenesis. We observed that lower serum BA concentration mainly in males is associated with neuroimaging markers of dementia, and pharmacological lowering of BA levels may be associated with higher risk of VaD in males. We hypothesize that dysregulation of BA signaling pathways in the brain may represent a plausible biologic mechanism underlying these results. Together, our observations suggest a novel mechanism relating abnormalities in cholesterol catabolism to risk of dementia.
Keyphrases
- positron emission tomography
- mild cognitive impairment
- computed tomography
- cognitive impairment
- pet ct
- magnetic resonance imaging
- signaling pathway
- white matter
- pet imaging
- resting state
- rheumatoid arthritis
- contrast enhanced
- low density lipoprotein
- cancer therapy
- mass spectrometry
- cerebral ischemia
- epithelial mesenchymal transition
- drug delivery
- cell proliferation
- blood brain barrier
- pi k akt
- endoplasmic reticulum stress
- data analysis
- diffusion weighted imaging
- subarachnoid hemorrhage