Study Investigates Genetic Predispositions to Dementia

Overview of Inherited Early-Onset Dementia

A recent study published in Nature Medicine explored the genetic factors contributing to the development of dementia. A prevalent form of inherited early-onset dementia primarily affects the frontal and temporal lobes of the brain, often resulting from mutations in the tau, granulin precursor (GRN), and chromosome 9 open reading frame 72 (C9orf72) genes. However, the precise mechanisms by which these genes lead to neuronal dysfunction and cell death remain unclear.

Research Methodology

In their study, Swarup and colleagues utilized mouse models to investigate the specific genetic processes involved in neurodegeneration. Rather than relying on a single inbred mouse strain, they examined three genetically distinct strains to enhance the applicability of their findings. The researchers monitored genetic activity in various regions of the degenerating mouse brain at different time intervals.

Key Findings

The study identified two gene clusters responsible for an excessive production of tau, a hallmark of neurodegenerative diseases such as dementia that contributes to brain cell death. Specifically, the researchers highlighted a microRNA module known as miR-203 that plays a regulatory role in the neurodegeneration process.

Exploring Therapeutic Approaches

Following their discoveries, Swarup and colleagues analyzed a database of experimental drugs to assess their effects on genetic mutations, seeking potential therapeutic options. When these drugs were tested on human cell cultures, they successfully halted dementia-induced neurodegeneration.

Implications for Future Research

Currently, there is no effective treatment that can stop the progression of dementia, making the research conducted by Swarup and colleagues crucial for advancements in neurodegenerative disease studies. While pharmaceutical companies typically focus on beta-amyloid in their therapeutic approaches, this study suggests that targeting tau may offer a new strategy for preventing brain deterioration associated with dementia. Although this research is still in its early stages, senior author Daniel Geschwind noted that “[…] this is an encouraging step.”

References

Swarup, V., Hinz, F., Rexach, J., Noguchi, K., Toyoshiba, H., & Oda, A. et al. (2018). Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia. Nature Medicine. doi: 10.1038/s41591-018-0223-3

Gordon, D. UCLA researchers discover genes tied to dementia in key early step toward new therapies. (2018). Retrieved from http://newsroom.ucla.edu/releases/ucla-gene-link-dementia-key-step-toward-new-therapies