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A tiny percentage of our DNA—around 2%—contains 20,000-odd genes. The remaining 98%—long known as the non-coding genome, or so-called ‘junk’ DNA—includes many of the “switches” that control when and how strongly genes are expressed.

Now researchers from UNSW Sydney have identified the DNA switches that help control how astrocytes work—these are brain cells that support neurons, and are known to play a role in Alzheimer’s disease.

In research published in Nature Neuroscience, researchers from UNSW’s School of Biotechnology & Biomolecular Sciences described how they tested nearly 1,000 potential switches—strings of DNA known as enhancers—in human astrocytes grown in the lab. Enhancers can be located very far away from the gene they control, sometimes hundreds of thousands of DNA letters away—making them difficult to study.

New York State Psychiatric Institute and Columbia University Medical Center investigators, with co-authors across additional US centers, report greater cognitive worsening at 78 weeks with valacyclovir than with placebo among adults with early symptomatic Alzheimer’s disease and herpes simplex virus (HSV) seropositivity.

Infectious diseases may contribute to Alzheimer’s disease pathogenesis. HSV-1 can become latent after oral infection, enter the brain via retrograde axonal transport, infiltrate the locus coeruleus, and migrate to the temporal lobe.

β-amyloid plaques and tau neurofibrillary tangles are neuropathological features of Alzheimer’s disease. Animal models connect HSV-1 infection of neuronal and glial cells with a decrease in amyloid precursor protein, an increase in intracellular amyloid β-protein, and phosphorylation of tau protein.

One specific state, referred to as State 4, emerged as a key point of difference between the two groups. This state was characterized by strong connections between the left and right hemispheres of the brain. It specifically involved robust communication between the temporal and parietal regions, which are areas often associated with language and sensory processing.

The data showed that children with autism spent considerably less time in State 4 compared to the typically developing children. They also transitioned into and out of this state less frequently. The reduced time spent in this high-connectivity state was statistically distinct.

The researchers then compared these brain patterns to clinical assessments of the children. They found a correlation between the brain data and the severity of autism symptoms. Children who spent the least amount of time in State 4 tended to have higher scores on standardized measures of autism severity.