Disparate and shared transcriptomic signatures associated with cortical atrophy in genetic bvFTD
Shen, T.; Vogel, J. W.; Van Deerlin, V. M.; Suh, E.; Dratch, L.; Phillips, J. S.; Massimo, L.; Lee, E. B.; Irwin, D. J.; McMillan, C. T.
Show abstract
Cortical atrophy in behavioral variant frontotemporal degeneration (bvFTD) exhibits spatial heterogeneity across genetic subgroups, potentially driven by distinct biological mechanisms. Using an integrative imaging-transcriptomics approach, we identified disparate and shared transcriptomic signatures associated with cortical thickness in C9orf72, GRN or MAPT-related bvFTD. Genes associated with cortical thinning in GRN-bvFTD were implicated in neurotransmission, further supported by mapping synaptic density maps to cortical thickness maps. Previously identified genes linked to TDP-43 positive neurons were significantly overlapped with genes associated with C9orf72-bvFTD and GRN-bvFTD, but not MAPT-bvFTD providing specificity for our associations. C9orf72-bvFTD and GRN-bvFTD shared genes displaying consistent directionality of correlations with cortical thickness, while MAPT-bvFTD displayed more pronounced differences in transcriptomic signatures with opposing directionality. Overall, we identified disparate and shared genes tied to regional vulnerability with increased biological interpretation including overlap with synaptic density maps and pathologically-specific gene expression, illuminating intricate molecular underpinnings contributing to heterogeneities in bvFTD.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Dysregulated coordination of MAPT exon 2 and exon 10 splicing underlies different tau pathologies in PSP and AD 95%
- Genome-wide association study and functional validation implicates JADE1 in tauopathy 94%
- Rare genetic variation in Fibronectin 1 (FN1) protects against APOEe4 in Alzheimer's disease 94%
Similar papers in this journal
- Spatially resolved transcriptomics reveals unique gene signatures associated with human temporal cortical architecture and Alzheimer's pathology 94%
- Regional differences in synaptic degeneration are linked to alpha-synuclein burden and axonal damage in Parkinson's disease and Dementia with Lewy bodies 94%
- Transcriptional profiling of Multiple System Atrophy cerebellar tissue highlights differences between the parkinsonian and cerebellar sub-types of the disease 94%
Similar papers in this journal
- Genome-wide consensus transcriptional signatures identify synaptic pruning linking Alzheimer's disease and epilepsy 94%
- Astrocyte biomarker signatures of amyloid-β and tau pathologies in Alzheimer’s disease 94%
- Tau pathology in the dorsal raphe may be a prodromal indicator of Alzheimer's disease 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.