Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n=237) data, combining both multiplexed proteomics CSF and genotype data, were used to assess the association between CSF analytes and risk SNPs in four genes (SNPs): GRN (rs5848), TMEM106B (rs1990622), ABCC9 (rs704180), and KCNMB2 (rs9637454).
Our data indicate that TT allele of rs5848 is associated with increased risk of AD, suggesting that genetic variant of progranulin gene may play an important role in AD development.
Similarly, the mRNA levels of granulin were decreased with respect to A allele of rs5848 in the inferior temporal cortex of neuropathologically confirmed AD patients.
However, stratification according to gender revealed a significant male-specific allele, genotype and haplotype association between AD and GRN SNPs rs4792939, rs850713, and rs5848.