Researchers have isolated the particular cell types likely to initiate common brain disorders and diseases, such as multiple sclerosis (MS) and Alzheimer’s disease, a finding that may point the way to new and targeted treatments.
The brain has a complex cellular architecture characterized by a diverse set of cell types that are highly interconnected. Identifying those involved with the pathogenesis of disease is particularly challenging in heterogeneous tissues where cell types are often poorly defined. In the majority of brain disorders, evidence exists for changes that affect multiple cell types.
In the study, titled “Identification of Vulnerable Cell Types in Major Brain Disorders Using Single Cell Transcriptomes and Expression Weighted Cell Type Enrichment” and recently published in the journal Frontiers in Neuroscience, scientists at the University of Edinburgh used an advanced gene analysis method, known as the Expression Weighted Cell-type Enrichment, to examine genes that switched on in certain types of brain cells. The information was then compared with genes known to be associated with conditions such as MS, Alzheimer’s, autism, schizophrenia and epilepsy, as well as anxiety disorders and intellectual disability.
Results showed that, for some of these diseases, support cells — rather than the neurons that transmit messages in the brain — are likely the first to be affected.
In Alzheimer’s, specifically, neurons are the focus of most treatment efforts because neuron damage is a disease hallmark. But the researchers found a different cell type — microglial cells — to be responsible for Alzheimer’s development and viewed neuron damage as a secondary symptom of disease progression. Developing drugs that directly target microglial cells could be a therapeutic option.
MS also demonstrated “strong evidence” for being primarily a microglial disorder, the researchers said. Microglia are resident immune cells of the central nervous system.
The strategy employed could also be used to develop new drugs for conditions with a genetic basis.
“We are in the midst of scientific revolution where advanced molecular methods are disentangling the Gordian Knot of the brain and completely unexpected new pathways to solving diseases are emerging. There is a pressing need to exploit the remarkable insights from the study,” Professor Seth Grant, who carried out the research with Dr. Nathan Skene, concluded in a press release.