Chromatin Accessibilty and Gene Expression of Frontotemporal dementia-associated Drosophila knock-in models

The clinical presentation of FTD is heterogeneous with patients exhibiting parkinsonism, dementia, atrophy in the temporal lobes, and personality changes. Treatments are limited to mitigating the behavioral changes associated with FTD as the underlying mechanisms causing the disease are still unclear.

Recent work in model systems and post-mortem tissue has shown that expression of FTD-associated Tau leads to epigenetic modifications that alter gene expression. We therefore used recently generated Drosophila knock-in models of FTD and single-cell sequencing techniques to identify chromatin accessibility and gene expression changes that are caused by specific FTD-associated Tau mutations. Comparing flies expressing wildtype human Tau (hTauWT) to flies expressing disease-associated mutant hTau (hTauK369I, hTauV337M, or hTauP301L) revealed differentially accessible regions in all cell populations, and notably many in the pericerebral fat body.