It is a known fact that the brain shrinks with age. However, research surrounding the underlying genetic causes behind the process is ongoing. Now, scientists from the University of Texas have discovered over 150 genes that play a role in the shrinkage of the brain's cortex—the outer layer regulating action, awareness and thinking.
According to the study, which used thousands of MRIs to map shrinkage of the brain, investigated several regions of the cortex. Dr. Sudha Seshadri, senior author of the study, said in a statement, "This is a very rich resource, and it will be mined for many years to understand the different associations we are seeing. We are excited to share it with the world."
Understanding the Process
Shrinkage of the brain is a natural biological process that accompanies aging. However, the pattern of shrinkage observed in healthy individuals varies from those who suffer from neurodegenerative diseases such as Parkinson's disease and Huntington's disease. The cortex region which consists mostly of grey matter— a collection of cells and networks— is affected by this shrinkage.
"We asked, 'What are the genes that seem to determine the thickness, area and volume of gray matter in these regions?'" said Dr. Seshadri. She added that such genes could provide new targets for the development of new drugs that could play an interventional role before the onset of clinical symptoms. Thus, the focus of the study revolved around the identification of such genes.
Identifying Genes Regulating Brain Shrinkage
For the study, the scientists analyzed 34 regions of the brain cortex in over 45,000 MRIs of healthy individuals. The first sample—the discovery sample—consisted of 22,894 individuals. It was from 20 study populations within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank.
After their analyses, they zeroed on 160 genes that they implicated in the process of the brain's shrinkage. According to Dr. Seshadri, the discovered genes were associated with crucial pathways in the brain that appear to be involved in its development, neurodegenerative and vascular diseases, and certain psychiatric disorders.
In order to replicate the findings, the team carried out the examination in another sample—replication sample— of 22,894 individuals. This sample was from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium.
Enabling Development of New Therapies
Talking about the importance of the finding, Dr. Claudia Satizabal, "This study has considerable statistical power. She added, "Because the results from the first sample were replicated in a second equally large sample, it is less likely that the results are purely due to chance."
The findings of the study can have significant implications in the development of the treatments for neurodegenerative diseases. "It is important to understand the biology of multiple regions of the cortex because each is affected differently in the various types of neurodegeneration including Alzheimer's disease," opined Dr. Seshadri.
However, the study was not without its limitations. One of them was the sample consisted of participants mostly of European ancestry. The other key limitations included variance in the analysis software, imaging instruments, and field strengths. "We seek to add other ethnicities to the CHARGE cohorts, including our Hispanic population of South Texas," concluded Dr. Seshadri.