Multi-functional PET imaging genetics in Alzheimer's disease

Objectives To use quantitative FDG and amyloid PET measurements mapping genetic risk factors in Alzheimer's disease.

Methods 76 subjects from ADNI GWAS dataset with more than 7 years following up PET scans using FDG, [18F]AV45, [11C]PIB, and MRI scans were collected in Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. The PLINK toolkit [1] was used for data processing and analysis. 539801 genotypes were selected from ADNI genetic dataset were used for analysis. All preprocessed PET images with structural MRIs were downloaded from ADNI database. All PET images were spatially normalized to MNI space using MRI and SPM8. 35 regions of interest (ROI) were manually drawing in a high resolution MRI template provided by VBM8 tool.Standard uptake values ratios (SUVR) to cerebellum were calculated. A general linear model to include age as a covariate was used for the correlation between each SNP genotype and ROI SUVRs.

Results The genotype rs1876152 on chromosome 5, genotype rs1501228 on chromosome 1, and genotype rs1946867 on chromosome 4 have significantly linear correlation with the measurements from FDG, [18F]AV45, [11C]PIB, respectively (p < 0.001).

Conclusions Our study first identified the three genotypes, rs1876152, rs1501228, and rs1946867, have significant correlation with FDG, [18F]AV45, [11C]PIB PET measurements, respectively. The evaluation of the 3 genotypes in monitoring AD progression will be followed with the ongoing ADNI study.