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. 2021 Jun 1;7:11. doi: 10.1038/s41514-021-00064-9

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Fig. 2 — Alterations in brain metabolite concentrations and brain gene expression related to cholesterol biosynthesis and catabolism in AD. Metabolites indicated in bold (non-italics) and in a box (e.g., Lanosterol) were measured and detectable in the study in the ITG and MFG in the BLSA and ROS cohorts. Genes indicated in bold and in a box (e.g., CYP46A1) were measured and detectable in the ERC, hippocampus, and visual cortex in GEO datasets. Metabolites or genes not in bold and not in a box (e.g., Lathosterol) were not measured or detectable. Genes indicated in a hexagon (e.g., HSD3B7) regulate reactions that are predicted by metabolic network modeling to be significantly different between AD and CN samples. a De novo cholesterol biosynthesis (pre-squalene mevalonate pathway). Acetyl CoA acetyl-coenzyme A, ACAT1 acetyl-coenzyme A acetyltransferase 1, ACAT2 acetyl-coenzyme A acetyltransferase 2, acetoacetyl CoA acetoacetyl-coenzyme A, HMGCS1 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1, HMG-CoA 3-hydroxy-3-methylglutaryl-coenzyme A, HMGCR 3-hydroxy-3-methylglutaryl-coenzyme A reductase, PMVK phosphomevalonate kinase, MVK mevalonate kinase, GGPPS1 geranylgeranyl diphosphate synthase 1, IDI1 isopentenyl-diphosphate delta isomerase 1, FDPS farnesyl-diphosphate synthase, IDI2 isopentenyl-diphosphate delta isomerase 2, FDFT1 farnesyl-diphosphate farnesyltransferase 1, SQLE squalene epoxidase, LSS lanosterol synthase. b De novo cholesterol biosynthesis (post-squalene mevalonate pathway, including the Bloch and Kandutsch–Russell pathways) and cholesterol esterification. DHCR24 24-dehydrocholesterol reductase, CYP51A1 cytochrome P450 family 51 subfamily A member 1, 24,25 DHLan 24,25-dihydrolanosterol, TM7SF2 transmembrane 7 superfamily member 2, SC4MOL methylsterol monooxygenase 1, SC5D sterol-C5-desaturase, DHCR7 7-dehydrocholesterol reductase, SOAT1 sterol O-acyltransferase 1. c Cholesterol catabolism (enzymatic). CYP27A1 cytochrome P450 family 27 subfamily A member 1, CYP3A4 cytochrome P450 family 3 subfamily A member 4, 4β-OHC 4β-hydroxycholesterol, 27-OHC 27-hydroxycholesterol, CH25H cholesterol 25-hydroxylase, CYP11A1 cytochrome P450 family 11 subfamily A member 1, 22R-OHC 22R-hydroxycholesterol, 25-OHC 25-hydroxycholesterol, CYP7B1 cytochrome P450 family 7 subfamily B member 1, 7α, 24-diOHC 7α, 24-dihydroxycholesterol, CYP46A1 cytochrome P450 family 46 subfamily A member 1, CYP7A1 cytochrome P450 family 7 subfamily A member 1, 24S-OHC 24S-hydroxycholesterol, CYP39A1 cytochrome P450, family 39, subfamily A member 1, 7a-OHC 7α-hydroxycholesterol, CYP8B1 cytochrome P450, family 8, subfamily B, member 1, 7α,12α-diOHCnone 7α,12α-dihydroxycholestenone, HSD3B7 3-beta-hydroxysteroid dehydrogenase type 7, 7α-OHCnone 7α-hydroxycholestenone, CA cholic acid, CDCA chenodeoxycholic acid. d Cholesterol catabolism (non-enzymatic). 7β-OHC 7β-hydroxycholesterol, 5α,6α-EC 5α,6α-epoxycholesterol, 5β,6β-EC 5β,6β epoxycholesterol, 5α,6β-EC 5α,6β epoxycholesterol.