With scientific technologies advancing, we learn more about the brain. And as modern medicine focuses more and more on personalized treatment of disease, including targeting the individual genetic makeup in which a disease manifests within a person, researchers are trying to understand the genetic profiles of neurological disorders and how they change over a person’s lifespan.
A research project that started in 2019 took on a large feat by collecting brain tissue from close to 1,500 people from several walks of life to build the largest map of gene activity to date — at least for one brain region, the prefrontal cortex. This area is where decision-making, planning, and emotional regulation take place, and local dysfunctions are linked to a wide variety of neurological diseases, including several types of dementia, Parkinson’s disease, and bipolar disorder.
The records and analysis encompass not one but eight different studies that were published at the same time, including three in Nature. The team has also decided to make all their work publicly available, inspiring other researchers to use their map to answer questions in the field, as this type of genetic profile of the human brain has previously been limited.
Recording Gene Activity in the Brain’s Executive Part
The monumental task aimed to find links between genetic changes, aging, and disease in certain brain areas. Because many neurological and psychiatric disorders arise from changes in the prefrontal cortex, the part of the brain in charge of higher executive functions, like planning, multitasking, and behavioral regulation, the researchers concentrated on this area, according to a summary in Nature.
Explore All OptionsThe map used postmortem brain tissue donations from almost 1,500 individuals, ranging from infants to people 108 years old. The donors represent a variety of ancestral backgrounds, as well as a mix of clinically healthy individuals and those with neurological diseases, including Alzheimer’s, Parkinson’s disease, schizophrenia, and bipolar disorder.
The tissue samples first underwent single-cell RNA sequencing, telling scientists which genes were activated in each cell at the time it was sampled and giving them an idea about the actual status of that cell. Overall, they measured gene activity in more than 6 million brain cells.
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Different Neurological Disorders Often Share the Same Molecular Changes
Using the recorded data on gene activity, the researchers started by mapping out how a subsection called the dorsolateral prefrontal cortex changes over time. They could identify three stages that depend on a person’s age. They describe how this brain area first drastically remodels itself when we’re young, stays stable through midlife, and then remodels again after the age of 65.
The researchers could also see how different brain cell types showed varying gene activity over those stages, including changes in immune activity, stress responses, and the internal biological clock. With this baseline of normal brain development in the prefrontal cortex, they could start to compare the data to samples from diseased individuals.
The team found that despite neurological disorders presenting with different mechanisms and symptoms, they often look similar on the molecular level. For example, when comparing the genetic activity of immune cells in Alzheimer’s and Parkinson’s disease, the scientists found that they share several genetic changes. Furthermore, in Alzheimer’s specifically, they could identify molecular pathways that connect it with behavioral symptoms often observed in people with the disease.
Accelerating Neurological Research With a Monumental Map
This is just the beginning of the questions that could be answered by using this vast map. The researchers hope that their large catalogue will support the development of more personalized treatments for neurological diseases, based on the genetic makeup a patient displays.
To accelerate the process, the researchers have made all the data and analytical instructions on how to use their records available to the public.
Overall, they summarize how the amount of data, including how different conditions in the same brain areas change molecularly over time, is a crucial leap for studying neurological diseases. They also hope to expand their map to other brain regions in the future.
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- This article references information from a study published in Nature: Landmark map of human brain’s gene activity holds clues to Alzheimer’s disease and more
