What is it and what does it include?
The researchers in this study performed a detailed analysis of the genetic activity in immune cells from individuals with a genetic variation associated with a brain disease called Frontotemporal Dementia (FTD), which is linked to a gene called MAPT. They compared the genetic activity in the immune cells of these FTD-related genetic variant carriers (8 individuals) to those of healthy individuals who didn't carry this genetic variation (another 8 individuals). The raw genetic data obtained from the sequencing was processed and aligned to a reference genome. To ensure the reliability of the data, various quality control measures were applied. After these quality control steps, they were left with data from around 181,000 cells for further analysis. This dataset specifically contains scRNA-seq data described here.
How can I use this dataset to advance my research?
This dataset is ideal for:
- Identification of Peripheral Biomarkers:
The study aimed to discover novel, blood-based biomarkers of tauopathy, including Frontotemporal Dementia (FTD). This research suggests that certain genes, such as CX3CR1, FCGR3A, and TMEM176A/B, show significant differential expression in individuals with a genetic variation associated with tauopathy. These genes could potentially serve as peripheral biomarkers not only for FTD but also for other neurodegenerative diseases, including Alzheimer's disease
- Connection Between Immune Cells and Tau Pathology:
The study found that changes in gene expression in specific immune cell types, such as monocytes and natural killer (NK) cells, may be associated with tau pathology. Since tau protein abnormalities are also observed in Alzheimer's disease, these findings suggest a potential link between immune cell activity and Alzheimer's-related tau pathology.
- NC Monocytes as a Common Marker:
The study highlighted a reduction in nonclassical (NC) monocytes in individuals with familial tauopathy. This reduction in NC monocytes has been observed in various neurodegenerative diseases, including ALS and Parkinson's disease. This finding may indicate a common peripheral marker of neurodegeneration that could extend to Alzheimer's disease, which shares some pathological features with these conditions.
- Potential for Peripheral Blood Biomarkers:
The study suggests that peripheral blood biomarkers, such as those identified in this research, have the potential to be easily collected and used for diagnosing neurodegenerative diseases. These biomarkers could provide a less invasive and more cost-effective alternative to current diagnostic methods, such as PET imaging or cerebrospinal fluid (CSF) collection.
- Future Research Directions:
The study acknowledges its limitations, including the small cohort size. To further advance our understanding of neurodegenerative diseases, including Alzheimer's, future research should replicate these findings in larger cohorts and explore whether similar peripheral immune responses are present in different forms of neurodegeneration. This research can help establish the role of peripheral immune responses in various proteinopathies and improve diagnostics and clinical trial tools.
Has this dataset helped researchers understand Alzheimer’s and other dementias better?
- AD & RNAseq:
In 2022, research findings from the Yokohama Lab suggested that the presence of the FTD-related genetic variation affects the genetic activity and abundance of certain immune cells, particularly monocytes and NK cells. These changes in immune cell activity may be linked to the development or progression of FTD. Additionally, specific genes like CX3CR1, nonclassical monocyte-related genes, and TMEM176A/B may play significant roles in the immune response related to FTD, and further investigation is needed to better understand their impact on neurodegenerative diseases associated with tau pathology. Doi: https://doi.org/10.1101/2022.10.28.514304
Data access can be requested via AD Workbench FAIR portal here. Access requests are reviewed by the team at UCSF Yokoyama Lab. Once your access has been provisioned, you will receive an email with instructions on how to access the data.
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