Immunity gene <i>IFITM3</i> variant: relation to cognition and Alzheimer pathology

Background IFITM3, an innate immune response protein and inhibitor of viral infection, was reported to modulate amyloid-β production in Alzheimer’s disease (AD). We aimed identify single-nucleotide polymorphisms (SNPs) IFITM3 associated with cognition AD biomarkers. Method used genetic, longitudinal biomarker data from Disease Neuroimaging Initiative (ADNI; N = 1,565) AddNeuroMed (N 633) as discovery replication samples, respectively. First, we performed gene-based association analysis SNPs cognitive performance. Second, SNP-based decline biomarkers amyloid positron emission tomography (PET), cerebrospinal fluid (CSF), magnetic resonance imaging (MRI). Result Gene-based showed that significantly performance (permutation-corrected p 1.25×10−3). Particularly, among two (rs10751647, rs2091850) performance, rs10751647 ADNI, which replicated AddNeuroMed. In addition, deposition measured by PET scan, CSF phosphorylated tau levels, entorhinal cortical thickness MRI scan ADNI. The Participants minor alleles (C) have less decline, burden, brain atrophy. eQTL is expression levels blood brain. Conclusion This suggests vulnerability for biomarkers, providing mechanistic insight regarding involvement activity infection AD.