Frontotemporal dementia

…Neurosciences studies inflammation in frontotemporal dementia through ON-FIRE (Open Network for Frontotemporal dementia Innovation Research), a UK-wide multi-centre study collecting data at more than 40 sites. The postholder leads statistical analysis and data management for blood biomarkers measured with SIMOA, NULISA, mass spectrometry and multiomics platforms, and builds pipelines linking samples to NHS digital records, longitudinal clinical data, genetics and MRI and PET neuroimaging. The work is computational analysis of blood-derive

…brain from Alzheimer's disease and frontotemporal dementia with tauopathy. Work covers procurement and characte

…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

…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

…lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS and FTD are two devastating, frequently co-occurring neurodegenerative disorders. While ALS primarily affects motor neurons, causing rapid progressive paralysis and premature death, FTD affects frontal and temporal lobes, leading to severe changes in personality, behaviour, or language skills. To characterise the contribution of inhibitory neurons to these phenotypes, we generated a mouse model based on the expression of mutant Fused in Sarcoma (FUS) selec

…Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). In particular, we aim to study the role of altered lipid metabolism and neuroinflammation in response to short (12 weeks) and prolonged (14-16 months) high-fat diet (H

…lateral sclerosis (ALS) and frontotemporal dementia (FTD), with a specific focus on the prevalent C9orf72 gene mutation. This mutation involves the expansion of a hexanucleotide repeat sequence - GGGGCC - transcribed in both sense (G4C2)n and antisense (C4G2)n directions, leading to the formation of nuclear RNA foci. A pivotal finding in our recent study is the discovery of an interaction between antisense C4G2 repeat RNA and phenylalanine-tRNA synthetase (FARS), resulting in diminished charging of phenylalanine-tRNA and consequ

…lateral sclerosis (ALS) and frontotemporal dementia (FTD), it is mislocalized and becomes a central component of cytoplasmic protein aggregates. Our aim was to investigate the interactome of wild-type TDP-43 and TDP-43 without nuclear localization signal (dNLS), which mimics a pathological condition in ALS. We generated inducible mammalian cell lines expressing TDP-43wt and TDP-TDP-43dNLS. Using the BioID method, we investigated the interactome of these

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are adult-onset neurodegenerative disorders that share common pathology and genetic causes. In many cases the RNA binding protein TDP-43 aggregates in the cytoplasm leading to the loss of its nuclear functions, including as a splicing repressor. This results in the erroneous inclusion of intronic sequences known as cryptic exons (CEs) in several mature mRNAs. Recently, it has been shown that TDP-43 depletion leads to CE inclusion in UNC13A, which encodes a protein crucial for priming synaptic vesicles for release. The UNC13A

…such as Alzheimer’s Disease and Frontotemporal Dementia. Decades before the onset of cognitive decline, many patients experience seizures which exacerbate the condition. Despite the recognised etiological overlaps between tauopathies and epilepsies, the relationship between tau and the development of circuit hyperexcitability is unclear and needs further investigation. Using wireless EEG to record intrahippocampal local field potentials (LFP), we characterised early biophysical alterations within the hippocampus of

…hallmarks of tauopathies, such as Frontotemporal Dementia (FTD), in the retina of patients even in the early stage of pathology. However, the precise molecular mechanisms and the direct sequence of events underlying this process remain poorly under

Traditionally, research on AMPA receptors has predominantly focused on GluA1 and GluA2 subunits. However, emerging consensus now emphasizes the pivotal role of GluA3 in specific forms of plasticity and behaviors. Though, most of the research conducted thus far has employed complete knockout animal model of GluA3-encoding gene (GRIA3) where compensatory events during neurodevelopment may obscure GluA3’s function.To better dissect GluA3's contribution to complex behaviors, we employed two in vivo mouse models of GluA3 downregulation in adult mice. First, we chronically administered autoantibodie

…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