Topic: Frontotemporal Dementia

Junjie Guo investigates how an intronic nucleotide-repeat expansion in C9orf72 causes familial and some sporadic cases of amyotrophic lateral sclerosis and frontotemporal dementia. The talk presents progress in understanding how the expansion changes gene expression, alongside functional-genomics approaches that identify potential therapeutic targets controlling expression of the pathogenic mutation. It also considers which mechanisms and modifiers extend to other disease-causing repeat expansions. Guo is Associate Professor of Neuroscience at Yale School of Medicine; the seminar is hosted by

A hallmark pathological feature of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion of RNA-binding protein TDP-43 from the nucleus of neurons in the brain and spinal cord. A major function of TDP-43 is as a repressor of cryptic exon inclusion during RNA splicing. By re-analyzing RNA-sequencing datasets from human FTD/ALS brains, we discovered dozens of novel cryptic splicing events in important neuronal genes. Single nucleotide polymorphisms in UNC13A are among the strongest hits associated with FTD and ALS in human genome-wi

The development of human induced pluripotent stem cells (iPSC) and their subsequent differentiation into neurons has provided new opportunities for the generation of physiologically-relevant, in vitro disease models. I will present our work using iPSC to modal familial Alzheimer's Disease (fAD) and Frontotemporal Dementia (FTD). We have investigated the mutation-specific effects of APP and PSEN1 mutations on Abeta generation in neurons generated from individuals with fAD, revealing distinct mechanisms that may contribute to clinical heterogeneity in disease. I will also discuss our work to und