<p>Frontotemporal lobar degeneration (FTLD) is one of the leading causes of dementia in individuals younger than 65 years, with the aggregation of <a href="https://www.ncbi.nlm.nih.gov/gene/23435">TDP-43</a> as one of the most common forms of FTLD. FTLD-TDP is clinically, genetically and pathologically heterogeneous, with <a href="https://www.ncbi.nlm.nih.gov/gene/2896">GRN</a> and <a href="https://www.ncbi.nlm.nih.gov/gene/203228">C9orf72 </a>as the most common genetic forms (although more than 50% of the cases are genetically unexplained), and A, B and C as the most common pathological subtypes. </p><p>To investigate the molecular differences between the different forms of FTLD-TDP, we performed bulk RNA sequencing (RNAseq) and reduced representation bisulfite sequencing (RRBS) from different brain regions of FTLD-TDP patients and controls. The RNAseq dataset includes samples from the frontal cortex of 149 individuals, comprising 127 FTLD-TDP cases (genetically unexplained types A (27), B (20) and C (22), 24 GRN mutation carriers, and 34 C9orf72 expansion carriers) and 22 controls. The RRBS dataset includes samples from the frontal cortex of 158 individuals —119 FTLD-TDP cases (genetically unexplained types A (25), B (24), and C (25), 20 GRN mutation carriers, and 25 C9orf72 expansion carriers) and 39 controls; and from the cerebellum of 151 individuals —113 FTLD-TDP cases (genetically unexplained types A (24), B (21), and C (23), 20 GRN mutation carriers, and 25 C9orf72 expansion carriers) and 38 controls. In total, the study consists of data from 183 unique individuals, with some overlap across the different datasets.</p>

RNA Transcriptomic and DNA Methylation Landscape in FTLD-TDP and Controls

Shared brain transcriptomic signature in TDP-43 type A FTLD patients with or without GRN mutations

Analysis of the splicing landscape of the frontal cortex in FTLD-TDP reveals subtype specific patterns and cryptic splicing