Home Mind & Brain New Technology Reveals Pathways to Tackle Alzheimer’s and Cognitive Decline

New Technology Reveals Pathways to Tackle Alzheimer’s and Cognitive Decline

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As humans age, the brain undergoes complex changes at the cellular level that can contribute to cognitive decline and neurodegenerative diseases like Alzheimer’s. But until now, the precise cellular mechanisms driving these age-related changes have remained largely mysterious.

A new study Nature explores the complexities of the ageing human brain at an unprecedented cellular level. The study introduces a new tool called Multinucleic Acid Interaction Mapping in Single Cells (MUSIC), which maps out gene expression, chromatin interactions, and RNA-chromatin associations in individual nuclei all at the same time. This revolutionary method offers new insights into the genetic and epigenetic mechanisms that could influence age-related diseases such as Alzheimer’s.

MUSIC technology provides a detailed map of chromatin architecture and transcription, allowing scientists to observe how these elements change with age. The study focused on 14 human frontal cortex samples from older donors, meticulously delineating diverse cortical cell types and states. One important finding was that there was a link between less short-range chromatin interactions and a transcriptomic signature that was “older” and related to Alzheimer’s disease pathology. This finding suggests a potential new pathway to understanding and possibly mitigating age-related cognitive decline.

Moreover, the study explored the role of gender in cellular ageing processes. Researchers found that the XIST non-coding RNA and chromosome X interacted in very different ways in female cortical cells. This has important implications for understanding why men and women are different in how likely they are to get diseases and how fast they age.

The use of MUSIC on these samples not only showed the expected differences in chromatin structure and gene expression between cells, but it also shed light on how chromatin architecture controls gene expression. This opens new avenues for research into the genetic foundations of neurodegenerative diseases and the effects of ageing at a cellular level.

For example, cells showing fewer chromatin interactions were associated with Alzheimer’s pathology, pointing to a direct link between chromatin organisation and disease progression. This could potentially lead to biomarkers or new therapeutic targets for the early detection and treatment of Alzheimer’s disease.

Another intriguing aspect of the MUSIC approach is its ability to highlight the differences in chromatin interactions across various cell types within the same tissue. This level of detail provides a richer understanding of the cellular heterogeneity in the human brain and its potential impact on individual susceptibility to age-related changes and diseases.

The implications of these findings are profound, extending beyond neuroscience to touch on aspects of personalised medicine and biotechnology. By mapping the interactions between chromatin and RNA within single cells, MUSIC paves the way for novel interventions that could one day prevent or reverse age-related cellular changes.

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