New Research Identifies Source of Cell Change in Alzheimer’s Disease

Researchers have identified that the expression change of a gene in specific cells in the human brain, called Microglia, may be associated with Alzheimer’s disease, according to a study published this week in the science journal PLoS ONE.

The expression of the gene, called ANK1 (ankyrin repeat domain-containing protein), was determined in three specific cell types — microglia, astrocytes, and neurons deriving from the hippocampus part of the brain of patients with Alzheimer’s disease.

It was identified by a research team, led by Arizona State University and the Translational Genomics Research Institute (TGen), via using an extremely precise method of isolating cells.

The team found that altered ANK1 expression originates in microglia, a type of immune cell found in the brain and central nervous system, according to the study.

In previous genetic and epigenetic-wide association studies, ANK1 has been identified as a potential risk factor for the development of Alzheimer’s disease, which is the most common cause of dementia.

However, “they were unable to identify the class of cells that may be responsible for such association because of the use of brain homogenates,” the study’s lead author Diego Mastroeni said in a press release.

“Here, we provide evidence that microglia are the source of the previously observed differential expression patterns in the ANK1 gene in Alzheimer’s disease,” said the assistant research professor at Biodesign’s ASU-Banner Neurodegenerative Disease Research Center.

The new research shows that in the hippocampus, a small looping structure shaped like a seahorse which is responsible for memory, ANK1 is four fold higher in the microglia of patients with Alzheimer’s disease.

Microglia is a type of immune cell found in the brain and key regulators of the inflammatory cascade typified in early Alzheimer’s development, according to the study.

“These findings emphasize that expression analysis of defined classes of cells is required to understand what genes and pathways are dysregulated in Alzheimer’s,” said Winnie Liang, an assistant professor, director of TGen Scientific Operations and director of TGen’s Collaborative Sequencing Center.

Furthermore, the study found that ANK1 was also significantly upregulated in the hippocampus microglia of Peritoneal Dialysis patients, and changes in ANK1, at least in microglia, may not be disease specific, but a response, or phenotype associated with neurodegeneration or neuroinflammation.

“The results obtained in this work emphasize the importance of methods that enable us to characterize the molecular profile of defined cells, either as a group or as single cells, that have been defined by any of several means,” said Paul Coleman, the study’s senior author.

Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and eventually the ability to carry out the simplest tasks.

In most people with Alzheimer’s, symptoms first appear in their mid-60s.

Estimates vary, but experts suggest that more than 5 million Americans may have Alzheimer’s, according to the US National Institutes of Health.

Alzheimer’s disease is currently ranked as the sixth leading cause of death in the United States, but recent estimates indicate that the disorder may rank third, just behind heart disease and cancer, as a cause of death for older people.

According to the World Health Organization, Alzheimer’s disease may contribute to 60-70 percent of dementia. (Xinhua)