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. 2009 Aug 4;18(1):44–53. doi: 10.1038/mt.2009.175

Figure 1.

Figure 1

Injections of AAV5-CYP46A1 vector in cerebral cortex and hippocampus of APP23 mice increase the level of 24S-hydroxycholesterol. (a) Representative expression of the wild-type (wtCYP46A1) and mutant (mtCYP46A1) forms of human CYP46A1 protein in the brain of 12-month-old APP23 mice after injection of adeno-associated vector (AAV) vector at 3 months. DG, dentate gyrus; Sbcl, subiculum; CA, Cornu Ammonis. Bar = 200 µmol/l. (b) Immunolabeling of hemaglutinin (HA)-tagged wtCYP46A1 protein in neurons (NeuN, nuclear staining, left panel) and co-localization with the endoplasmic reticulum Grp78 Bip marker (right panel). HA-tagged mtCYP46 protein has identical subcellular localization (data not shown). Bar = 200 µmol/l. (c) Cholesterol and 24S-hydroxycholesterol concentrations in the cerebral cortex and hippocampus of 12-month-old APP23 mice injected with AAV5-wtCYP46A1 or AAV5-mtCYP46A1 vectors (n = 5 mice per group). No difference in 24S-hydroxycholesterol and cholesterol content was observed between noninjected and AAV5-mtCYP46A1-injected APP23 mice. (d) Quantitative expression of murine 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr), sterol-binding protein 2 (Srebp2), acyl-coenzyme A: cholesterol acyltransferase 1 (Acat1), low-density lipoprotein–related protein 1 (Lrp1), lecithin:cholesterol acyltransferase (Lcat), and Niemann–Pick disease C1 (Npc1) genes in APP23 mice at 12 months after cerebral injections of AAV5-wtCYP46A1 or AAV5-mtCYP46A1 vectors (n = 5 mice per group). (Mann–Whitney U-test) ***P < 0.0005; NS, non significant.