Expression of Novel Alzheimer’s Disease Risk Genes in Control and Alzheimer’s Disease Brains

<div><p>Late onset Alzheimer’s disease (LOAD) etiology is influenced by complex interactions between genetic and environmental risk factors. Large-scale genome wide association studies (GWAS) for LOAD have identified 10 novel risk genes: <em>ABCA7</em>, <em>BIN1</em>, <em>CD2AP</em>, <em>CD33</em>, <em>CLU</em>, <em>CR1</em>, <em>EPHA1</em>, <em>MS4A6A</em>, <em>MS4A6E</em>, and <em>PICALM</em>. We sought to measure the influence of GWAS single nucleotide polymorphisms (SNPs) and gene expression levels on clinical and pathological measures of AD in brain tissue from the parietal lobe of AD cases and age-matched, cognitively normal controls. We found that <em>ABCA7, CD33,</em> and <em>CR1</em> expression levels were associated with clinical dementia rating (CDR), with higher expression being associated with more advanced cognitive decline. <em>BIN1</em> expression levels were associated with disease progression, where higher expression was associated with a delayed age at onset. <em>CD33, CLU,</em> and <em>CR1</em> expression levels were associated with disease status, where elevated expression levels were associated with AD. Additionally, <em>MS4A6A</em> expression levels were associated with Braak tangle and Braak plaque scores, with elevated expression levels being associated with more advanced brain pathology. We failed to detect an association between GWAS SNPs and gene expression levels in our brain series. The minor allele of rs3764650 in <em>ABCA7</em> is associated with age at onset and disease duration, and the minor allele of rs670139 in <em>MS4A6E</em> was associated with Braak tangle and Braak plaque score. These findings suggest that expression of some GWAS genes, namely <em>ABCA7</em>, <em>BIN1</em>, <em>CD33</em>, <em>CLU</em>, <em>CR1</em> and the <em>MS4A</em> family, are altered in AD brains.</p>