NEW FINDINGS — NEUROSCIENCE
How Hidden DNA Switches Might Protect Your Brain Scientists are cracking the code on a major brain mystery: why a protein called tau goes rogue and clumps together in diseases like Alzheimer’s and Parkinson’s. Normally, tau helps keep brain cells stable, but when it builds up too much, it can destroy them. Scientists wanted to understand how the gene encoding tau ( MAPT ) is controlled and if certain parts of the DNA near the gene could play a role in brain diseases. The researchers used advanced tools to study brain cells in the lab and post-mortem brain tissue. They looked for “cis-regulatory elements” (CREs), which are special DNA regions that help control gene activity by telling the brain when to make more tau. By mapping how DNA folds and connects, they found several CREs that were far away from the MAPT gene but still physically interact to turn it on or off. The team tested these CREs to see if they could activate MAPT and found that some regions were essential for tau production. They also looked at DNA from people with and without neurodegenerative diseases. They discovered that rare genetic changes in these CREs may actually protect against diseases by lowering tau production. This study highlights the importance of CREs in con- trolling tau levels in the brain. Understanding these regions better has the potential to help scientists develop new therapies for Alzheimer’s and related diseases by reducing tau production and its harmful effects. n REFERENCE: Rogers, B.B., et al. Neuronal MAPT expression is mediated by long-range interactions with cis-regulatory elements. American Journal of Human Genetics [2024] 111(2):259-279. https://doi.org/10.1016/j.ajhg.2023.12.015
Mitochondria Spit DNA into Brain Cells In addition to the large amounts of DNA found inside our cells’ nucleus, a smaller, circular strand of DNA is present within our cells’ mitochondria. This mitochondrial DNA (mtDNA) is usually maintained separately from nuclear DNA, but the transfer of mitochondrial DNA into nuclear DNA has been documented. Nuclear mitochondrial DNA (NUMT) is a sequence of mtDNA that has been expelled and integrat- ed into the nuclear genome. During this process, mtDNA acts like a virus, cutting nuclear DNA and inserting itself as the cut is repaired. The human genome shows evidence of accumulating NUMTs over time, most of which occur in noncoding regions and are thought to have little functional impact. This phenomenon was previously considered rare and mostly inconsequential. However, a 2024 study revealed that NUMTs occur more frequently in the human brain than in other body tissues. Even within the brain, certain regions had more NUMTs, suggesting that these transfers occur spontaneously during brain development or throughout life. These NUMTs may impact brain aging and lifespan, as researchers found that individuals with more NUMTs in their prefrontal cortex tended to die earlier than those with fewer. NUMTs are also frequently found in cancer cells, where they may contribute to genetic instability. Their accumulation in the brain could similarly disrupt genomic integrity and affect neural function. This connection emphasizes the need to further explore how NUMTs influence cellular aging and their role in neurodegenerative diseases. Scientists used cultured human skin cells to measure the rate of new mitochondrial DNA transfers. They found that new mito- chondrial DNA transfers into the genome occurred every 3–14 days. However, when cells were exposed to mitochondrial stress, NUMTs accumulated 4–5 times faster, indicating a connection between mitochondrial health and genomic stability. This ongoing transfer of mtDNA into the nuclear genome over our lifetime adds to the grow- ing understanding of mito-nuclear communication mechanisms that help shape human health. n REFERENCE: Zhou, W. et al. Somatic nuclear mitochondrial DNA insertions are prevalent in the human brain and accumulate over time in fibroblasts. PLoS Biology [2024] 22(8):e3002723. https://doi.org/10.1371/journal.pbio.3002723 placebo. The treatment also lowered the risk of progressing to more advanced stages by up to 39%. On average, amyloid plaques were reduced by 84% after 18 months of treatment, with the most signifi- cant benefits observed in individuals in the early stages of the disease. By directly targeting amyloid plaques, Kisunla offers a more focused approach to slowing disease progression and improving patients' quality of life. However, the cost of treatment is a critical factor. The financial burden on patients and healthcare systems is consider- able with a list price of approximately $696 per vial, or around $32,000 annually. Traditionally, Alzheimer’s treatments have only been able to focus on symptom management. Kisunla, along with other emerging therapies, represents a shift toward addressing the underlying causes of the disease, offering new hope for those affected. n
The laboratory of HudsonAlpha faculty researcher Nick Cochran, PhD, contributed to this work.
Plaque Busting Alzheimer’s Treatment
Alzheimer's disease is a progressive brain disorder that gradually impairs a person’s ability to think, remember, and perform daily tasks. It is the seventh leading cause of death in the United States. Alzhei- mer’s disease is characterized by the accumulation of amyloid protein plaques between neurons and tau protein tangles within neurons. In July 2024, the FDA approved the drug Kisunla ™ for treating early-stage Alzheimer's disease. Kisunla is an antibody-based therapy that binds to amyloid beta plaques, helping the immune system clear them from the brain. Administered through a monthly intravenous infusion, treatment continues until the plaques are removed. Clinical trials showed that patients receiving Kisunla experienced up to a 35% reduction in cognitive and functional decline compared to those on a
REFERENCE: U.S. Food and Drug Administration. FDA approves treatment for adults with Alzheimer’s disease. [2024] https://www.fda.gov/drugs/news-events-human- drugs/fda-approves-treatment-adults-alzheimers-disease
12
Made with FlippingBook - Online magazine maker