Hidden roots: how dementia genes might impact the brain long before disease
Like a tree whose growth is shaped by its genetic blueprint long before its branches spread wide and its final form becomes visible, the human brain is also influenced by genetics from the very beginning of life. Many of these early influences are hidden in that they do not cause obvious problems or symptoms, yet they may subtly shape how the brain develops and play a crucial role in disease development later on in life. Understanding these hidden early effects may allow us to better explain later-life brain disorders like dementia, which are known to be influenced by genetics.
A recent study conducted by researchers at Western University investigated a particular type of dementia called frontotemporal dementia. Frontotemporal dementia is characterized by changes in behaviour, personality, and language, with symptoms typically beginning to show between the ages of 45 and 65; therefore, this disease is not usually considered relevant to younger adults. This study examined gene mutations that are associated with frontotemporal dementia. Gene mutations are small changes in DNA, the body’s instruction manual, that can impact how cells and organs function. For example, gene mutations in an apple tree’s DNA could lead to a change in the taste, colour, or size of the apples that are produced when the tree is fully grown.
In this study, the researchers explored whether specific genes might influence the brain before frontotemporal dementia symptoms appear. The ages of study participants ranged from 18 to 89.7 years. Two genes of interest in this study were the GRN gene and the MAPT gene, both known to be associated with frontotemporal dementia based on prior research. The researchers used MRI brain imaging to measure total intracranial volume, which is the amount of space inside the skull that the brain occupies. Total intracranial volume is a marker of early brain development as it is largely established in childhood. This measurement remains relatively stable throughout adulthood and is thus not a reflection of changes due to aging or disease later in life.
The researchers found that adults with mutations in the GRN gene and the MAPT gene showed subtle differences in total intracranial volume compared with familial relatives who did not carry the mutation. Specifically, mutations in the GRN gene were found to be associated with larger total intracranial volumes, while mutations in the MAPT gene were found to be associated with smaller total intracranial volumes. These findings suggest that mutations in some genes linked to frontotemporal dementia may influence brain structure during early development and potentially affect brain function long before disease onset.
In conclusion, although frontotemporal dementia typically presents between the ages of 45 and 65, the GRN and MAPT genes appear to influence brain development much earlier in life. Just as redwood trees are destined to grow tall, whereas willows will develop graceful, arching branches—despite their saplings initially appearing similar—diseases like dementia may also be shaped by genetic influences on the human brain that are inconspicuous in early life. Understanding these changes could help us better grasp how frontotemporal dementia develops and whether early interventions might one day be possible.