Cholesterol‐related APOB Thr98Ile correlates with brain cortical APOB mRNA levels

Background Apolipoprotein B (APOB) is well-known for its role in cholesterol metabolism. We recently showed that APOB protein levels are elevated the CSF of patients suffering from sporadic Alzheimer’s disease (AD) compared to control individuals (Picard et al, Alzheimers Dement. https://doi.org/10.1002/alz.12442). Since rare coding variants were discovered association with early-onset familial (Wingo JAMA Neurol. 2019), we hypothesized common could influence molecular mechanisms leading AD. Method Publicly available genomic and transcriptomic data screened possible interactions between single nucleotide polymorphisms (SNPs) brain mRNA levels. Potential regulatory SNPs contrasted blood obtained Global Lipids Genetics Consortium (GLGC), order highlight their systemic effects. Brain tissue measured frontal cortices autopsy-confirmed controls AD subjects Douglas-Bell Canada Bank (DBCBB) using high performance liquid chromatography (HPLC). DNA extracted those samples was used perform locus genotyping help Illumina Screening Array (GSA) chip. Result The Thr98Ile variant commonly associated hypercholesterolemia found correlate a significant reduction cortical three different cohorts. In GLGC cohort, this SNP strongly associates LDL-cholesterol 188 578 (p = 9.48E-183). Our preliminary analysis shows also correlates (r2 0.36; p < 0.005) samples. Using public databases genotypic AD-related neuropathological data, inconsistent associations pathophysiological changes brain. Ongoing studies our laboratory examining impact on relation classical pathological markers large group subjects. Conclusion Although significantly gene regulation samples, effect neuropathology remains be clearly defined subject current investigations.