IC‐P‐030: In Vivo Nadh Fluorescence Imaging of Double Transgenic Ad Mice Reveals Chronic Tissue Hypoxia

terol, and participate in neuroinflammatory processes. CYP activity is also implicated in Alzheimer’s disease (AD), particularly in amyloid-b (Ab) accumulation in CSF. We examined whether genetic polymorphisms of CYP are associated with AD pathology. Methods: [18F]florbetapir-PET imaging was employed to assess brain Ab levels in 256 subjects from a discovery cohort (ADNI: 186CN, 105 lMCI, 47AD). Linear regression models examined the association of 30 SNPs from four genes of CYP (CYP3A4, CYP2C9, CYP2C19 and CYP1A1) with global [18F]florbetapirSUVR, adjusting for age, sex, and ApoE-e4carriage status. Significant signals were interrogated at the voxel level using RMINCtool, and, separately, tested for associations with CSF Ab and Ab/p-tau ratio. Neuropathologic data from the Rush ROS and MAP cohorts were used to generalize the findings to Ab load and PHFtau tangle density by immunocytochemistry in post-mortem brains (302 CN, 180 aMCI, 259 AD). Results: The analysis of [18F]florbetapir identified an intronic variant in the CYP2C19 gene (rs4388808; P1⁄40.0005), in which carriers of the minor-allele (G) had lower global SUVR (Figure 1). The voxel-wise analysis showed a significant effect of the SNP in the frontal and posterior cingulate cortices, as well as in the inferior parietal cortex (Figure 2). Carriers of the minor-allele were also associated with higher CSF Ab (P1⁄40.003) and higher Ab/p-tau ratio (P1⁄40.01). In postmortem brains, minor-allele carriers had a lower Ab load (P1⁄40.04), lower PHFtau tangle density (P1⁄40.03) as well as better episodic memory (P1⁄40.008). Conclusions: The rs4388808, an intronic variant of the CYP2C19 gene is implicated in Ab load, tau pathology and episodic memory, where the minor-allele protects against AD pathology.