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Researchers at the University of California San Diego have come up with a groundbreaking method, MUSIC (multinucleic acid interaction mapping in single cells), revealing intriguing insights into the aging process of brain cells and its connection to Alzheimer's disease, as well as uncovering gender-specific patterns in cognitive decline.

The study, detailed in a paper published in Nature, showcases the innovative potential of MUSIC in unraveling the complexities of neurodegenerative diseases like Alzheimer's. This cutting-edge technique enables researchers to delve into individual brain cells, mapping out interactions between chromatin and RNA, pivotal components governing cellular functions.

Lead author Sheng Zhong, a professor in the Shu Chien-Gene Lay Department of Bioengineering at UC San Diego, highlights the transformative capabilities of MUSIC in exploring novel molecular mechanisms underlying Alzheimer's pathology, offering prospects for targeted therapeutic interventions and enhanced patient outcomes.

"The technology has the potential to help us uncover novel molecular mechanisms underlying Alzheimer's pathology, which could pave the way for more targeted therapeutic interventions and improved patient outcomes," Zhong said, Neuroscience News reported.

Through the analysis of postmortem brain samples, particularly human frontal cortex tissues, the research team identified distinct patterns of interactions between chromatin and RNA in different types of brain cells. Notably, cells exhibiting fewer short-range chromatin interactions displayed signs of aging and Alzheimer's disease, with affected individuals exhibiting a higher proportion of these aged brain cells compared to healthy counterparts.

"With this transformative single-cell technology, we discovered that some brain cells are 'older' than others," Zhong noted.

"If we could identify the dysregulated genes in these aged cells and understand their functions in the local chromatin structure, we could also identify new potential therapeutic targets," said study co-first author Xingzhao Wen, a bioinformatics Ph.D. candidate in Zhong's lab.

Moreover, the study unveils gender-specific differences in brain cell aging, particularly in the cortex of female mice, where a higher ratio of aged oligodendrocytes to aged neurons was observed. This finding suggests potential implications for the increased risks of neurodegenerative disorders observed in women, highlighting the need for further investigation into gender-specific factors influencing cognitive decline.

"The disproportionate presence of old oligodendrocytes in the female cortex could shed new light on the increased risks of neurodegenerative and mental disorders observed in women," said Wen.

Moving forward, researchers aim to optimize MUSIC for identifying regulatory genes and circuits responsible for accelerated brain cell aging, with the ultimate goal of developing strategies to mitigate brain aging and combat neurodegenerative diseases like Alzheimer's.