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The Rohn lab publishes study highlighting link between dementia risk and APOE4 allele

Picture of Troy at miscroscope

Troy Rohn, a professor in the Department of Biological Sciences, was recently published in Frontiers of Aging Neuroscience for novel Alzheimer’s Disease research related to the Apolipoprotein E (ApoE4). The APOE gene comes in several different forms, or alleles. Each person inherits two APOE alleles, one from each biological parent. Possessing the APOE4 is the single most important genetic risk factor for late-onset Alzheimer’s disease.

The newly published study is titled “Transcriptome Analyses in BV2 Microglial Cells Following Treatment With Amino-Terminal Fragments of Apolipoprotein E.”

The study supports the link between the increased dementia risk and APOE4 may be due to enhanced inflammation via activation of microglia through gene expression. Microglia are white blood cells which function as a major line of immune defense for the central nervous system.

“Despite this known risk, it is not well understood how the protein expressed actually increases the risk for dementia at the molecular level. The normal role of APOE is to shuttle cholesterol around in the brain. We now show that the ApoE4 protein is clipped and a resulting fragment is able to traffic to the nucleus in microglia. Here it acts as a transcription factor leading to the expression of thousands of genes, many related to immune function and inflammation,” explained Rohn. “This was a very surprising result for a protein that normally has a pretty mundane function in the brain.”

According to Rohn, APOE4 is present in 10-15 percent of people, yet this allele is present in a majority of all known Alzheimer’s Disease cases (40-65 percent).

chart showing how allele impacts likelihood of Alzheimer's
Risk of susceptibility, based on alleles., CC BY-SA

Learn more about Rohn’s research here.