What is it and what does it include?
Hexanucleotide repeat expansion (HRE) within C9orf72 is the most common genetic cause of frontotemporal dementia (FTD). Thalamic atrophy occurs in both sporadic and familial FTD but is thought to distinctly affect HRE carriers. Separately, emerging evidence suggests widespread de-repression of transposable elements (TEs) in the brain in several neurodegenerative diseases, including C9orf72 HRE-mediated FTD (C9-FTD). Whether TE activation can be measured in peripheral blood and how the reduction in peripheral C9orf72 expression observed in HRE carriers relates to atrophy and clinical impairment remain unknown.
In this study, investigators generated a novel, whole-blood RNA-seq dataset to determine the relationships between peripheral C9orf72 (a gene that provides instructions for making a protein that is found in various tissues) expression, TE activation, thalamic atrophy, and clinical severity. The study included normal controls and C9orf72 HRE carriers.
How can I use this dataset to advance my research?
This dataset is ideal if:
- you’re studying peripheral blood RNA sequencing (RNA-seq) data and neuroimaging analyses from C9orf72 HRE carriers from across the clinical spectrum and healthy controls to:
- confirm global thalamic atrophy and reduced peripheral expression of C9orf72 in HRE carriers.
- identify disproportionate atrophy of specific thalamic nuclei in HRE carriers.
- show that peripheral C9orf72 expression associates with clinical impairment independent of thalamic atrophy.
- discover global peripheral de-repression of TEs in affected HRE carriers.
- demonstrate strikingly increased expression of the human-specific LINE1 element, L1HS, in symptomatic HRE carriers.
- show that peripheral L1HS levels associate with thalamic nuclei volumes in FTD-relevant regions.
Has this dataset helped researchers understand Alzheimer’s and other dementias better?
Of course!
- AD & Radiogenomics:
In 2022, research showed that de-repression of TE expression in C9-ALS/FTD patients is not restricted to the central nervous system (CNS). Peripheral upregulation of TEs such as L1HS may therefore enable novel, blood-based biomarkers for C9-ALS/FTD.. July 2022 – DOI: https://doi.org/10.1101/2022.07.28.501897
