The study discovered that as Widely-Held Alzheimer’s disease progresses, brain levels of enzymes that regulate DNA-folding decrease.

New Study Calls Into Question Widely-Held Alzheimer’s Beliefs

Researchers from the University of Pittsburgh, McGill University, and Harvard University found that, in contrast to earlier research, the levels of brain enzymes that control DNA folding drop as Widely-Held Alzheimer’s disease worsens. Their findings were recently published in the journal Nature Communications. These dogma-challenging findings show that decreased levels of Histone Deacetylase I (HDAC I), one of the enzymes that control how DNA is packaged inside the cell’s nucleus, are associated with the negative effects of misfolded beta-amyloid and tau proteins and Alzheimer’s disease-associated cognitive decline. These results were verified across two independent cohorts of live patients with Alzheimer’s disease as well as on post-mortem brain tissues. Alzheimer’s disease is a deadly neurodegenerative disease that typically affects the elderly but begins decades before symptoms appear. Forty-four million people live with Alzheimer’s disease or associated dementia. Alzheimer’s patients develop cognitive impairments over time, including memory loss and difficulty thinking and speaking, due to the formation of plaques of misfolded beta-amyloid and tangled strands of tau proteins, which induce nerve cell death and brain tissue damage. However, amyloid and tau disorders are just one piece of the complex picture. Over the last few decades, researchers have started to focus on additional processes—neuroinflammation and changes in the chemical environment of the brain cells—and how these might impact the development of the condition.

One of these processes is known as epigenetic histone modification. A cell may adjust the efficiency with which genetic information is translated into templates for new proteins by modifying how DNA is folded within its nucleus—whether it is tightly wrapped around protein barrels called histones or hung in looser threads. This permits the cell to swiftly and reversibly modify the way our genes operate and react to changes in the environment without changing the DNA sequence itself. In the long quest to develop safe, effective therapies that stave off cognitive decline and reverse disease progression, a subtype of enzymes that drive epigenetic modifications—HDACs—emerged as promising targets for new Alzheimer’s therapies.HDACs carry on a chemical reaction that encourages tighter packing of DNA molecules into condensed bundles and restricts biosynthesis of new proteins in response to environmental cues. Earlier studies on post-mortem brain samples reported that levels of HDACs in the brains of patients with Widely-Held Alzheimer’s increase as the disease progresses. High levels of HDACs were thought to restrict the brain’s ability to produce new functional proteins that make up critical cell components and, therefore, contribute to memory loss and cognitive decline. The new paper, however, challenges the status quo and adds another piece to an already confusing picture. The loss of HDAC I might be mechanistically linked with the emergence of beta-amyloid and tau pathologieswhich, as Pascoal and colleagues showed in their previous paper, are intertwined with brain tissue inflammation and drive Alzheimer’s disease progression and precede cognitive changes that accompany the disease.

Source: This news is originally published by scitechdaily

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