A5007886181- Genetic Neurodegenerative Diseases
- Neurological disorders and treatments
- Mitochondrial Function and Pathology
- Advanced Neuroimaging Techniques and Applications
- Functional Brain Connectivity Studies
- Advanced MRI Techniques and Applications
- Parkinson's Disease Mechanisms and Treatments
- Visual Attention and Saliency Detection
- Tryptophan and brain disorders
- Neuroscience and Neuropharmacology Research
- Face Recognition and Perception
- Medical Image Segmentation Techniques
- Face recognition and analysis
- Sepsis Diagnosis and Treatment
- Systemic Sclerosis and Related Diseases
- Neurology and Historical Studies
- Botulinum Toxin and Related Neurological Disorders
- Visual perception and processing mechanisms
- Muscle metabolism and nutrition
- Biomedical and Engineering Education
- Neuroinflammation and Neurodegeneration Mechanisms
- Chemokine receptors and signaling
- Cell Image Analysis Techniques
- Hereditary Neurological Disorders
- Biomedical Ethics and Regulation
University College London
2014-2022
National Hospital for Neurology and Neurosurgery
2017-2022
Huntington's Disease Association
2017-2022
University of Iowa
2021
John Wiley & Sons (United States)
2020
Vanderbilt University Medical Center
2020
Hudson Institute
2020
The Ohio State University
2020
Sahlgrenska University Hospital
2018
Sorbonne Université
2018
Huntington's disease (HD) is a genetic progressive neurodegenerative disorder, caused by mutation in the HTT gene, for which there currently no cure. The identification of sensitive indicators progression and therapeutic outcome could help development effective strategies treating HD. We assessed mutant huntingtin (mHTT) neurofilament light (NfL) protein concentrations cerebrospinal fluid (CSF) blood parallel with clinical evaluation magnetic resonance imaging premanifest manifest HD...
Disease-modifying treatments are in development for Huntington's disease; crucial to their success is identify a timepoint patient's life when there measurable biomarker of early neurodegeneration while clinical function still intact. We aimed this novel cohort young adult premanifest disease gene carriers (preHD) far from predicted symptom onset.
BackgroundThe earliest white matter changes in Huntington's disease are seen before onset the premanifest stage around striatum, within corpus callosum, and posterior tracts. While experimental evidence suggests that these may be related to abnormal gene transcription, we lack an understanding of biological processes driving this regional vulnerability.MethodsHere, investigate relationship between transcription healthy brain, using Allen Institute for Brain Science transcriptome atlas,...
Longitudinal analysis in 80 patients shows that mutant huntingtin and neurofilament light could predict Huntington’s disease progression.
Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration number conditions, including Huntington disease (HD). This study investigates the regional distribution NfL-associated neural pathology HD gene expansion carriers.
Abstract Objective Determining the sequence in which Huntington's disease biomarkers become abnormal can provide important insights into progression and a quantitative tool for patient stratification. Here, we construct present uniquely fine‐grained model of temporal from premanifest through to manifest stages. Methods We employ probabilistic event‐based determine appearance atrophy brain volumes, learned structural MRI Track‐ HD study, as well estimate uncertainty ordering. use longitudinal...
Abstract Objectives: Visuospatial processing deficits have been reported in Huntington’s disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings HD. Methods: We compared 119 premanifest (55> 64<10.8 years to expected onset) 104 early symptomatic (59 stage-1 45 stage-2) gene carriers, with 110 controls on visual search mental rotation performance at baseline 12 months. In the groups, we also task severity, functional capacity...
BackgroundCharacterizing changing brain structure in neurodegeneration is fundamental to understanding long-term effects of pathology and ultimately providing therapeutic targets. It well established that Huntington's disease (HD) gene carriers undergo progressive changes during the course disease, yet trajectory cortical atrophy not defined. Given genetic therapies currently tested HD are primarily expected target cortex, across this region essential.MethodsCapitalizing on a unique...
We lack a mechanistic explanation for the stereotyped pattern of white matter loss seen in Huntington's disease (HD). While earliest changes are around striatum, within corpus callosum, and posterior tracts, order which these occur why connections specifically vulnerable is unclear. Here, we use diffusion tractography longitudinal cohort individuals yet to develop clinical symptoms HD identify hierarchy vulnerability, where topological length between brain area its neighbors predicts rate...
Objective Huntington's disease (HD) gene carriers can be identified before clinical diagnosis; however, statistical models for predicting when overt motor symptoms will manifest are too imprecise to useful at the level of individual. Perfecting this prediction is integral search modifying therapies. This study aimed identify an imaging marker capable reliably real‐life diagnosis in HD. Method A multivariate machine learning approach was applied resting‐state and structural magnetic resonance...
The initial stages of neurodegeneration are commonly marked by normal levels cognitive and motor performance despite the presence structural brain pathology. Compensation is widely assumed to account for this preserved behaviour, but apparent simplicity such a concept, it has proven incredibly difficult demonstrate phenomenon distinguish from disease-related Recently, we developed model compensation whereby activation, behaviour pathology, components key understanding compensation, have...
Objectives Cognitive flexibility, which is key for adaptive decision-making, engages prefrontal cortex (PFC)-striatal circuitry and impaired in both manifest premanifest Huntington’s disease (pre-HD). The aim of this study was to examine cognitive flexibility a far from onset pre-HD cohort determine whether an early impairment exists if so, fronto-striatal circuits were associated with deficit. Methods In the present study, we examined performance 51 participants (mean age=29.22 (SD=5.71)...
Pathological processes in Huntington's disease (HD) begin many years prior to symptom onset. Recently we demonstrated that a premanifest cohort approximately 24 from predicted onset, despite intact function, there was evidence of subtle neurodegeneration. Here, use novel imaging techniques determine whether macro- and micro-structural changes can be detected across the whole-brain same cohort. 62 HD (PreHD) 61 controls Young Adult Study (HD-YAS) were included. Grey white matter volume,...
The selection of an appropriate segmentation tool is a challenge facing any researcher aiming to measure grey matter (GM) volume. Many tools have been compared, yet there currently no method that can be recommended above all others; in particular, lack validation disease cohorts. This work utilises clinical dataset conduct extensive comparison tools. Our results confirm advantages and disadvantages, we present series considerations may use when selecting method, rather than ranking these...
Abstract Converging lines of evidence from several models, and post‐mortem human brain tissue studies, support the involvement kynurenine pathway (KP) in Huntington's disease (HD) pathogenesis. Quantifying KP metabolites HD biofluids is desirable, both to study pathobiology as a potential source biomarkers quantify dysfunction evaluate biochemical impact therapeutic interventions targeting its components. In prospective single‐site controlled cohort with standardised collection cerebrospinal...
<h3>Background and Objectives</h3> Longitudinal measurements of brain atrophy using structural MRI (sMRI) can provide powerful markers for tracking disease progression in neurodegenerative diseases. In this study, we use a model to learn individual-level times hence reveal new timeline sMRI changes Huntington (HD). <h3>Methods</h3> We data from the 2 largest cohort imaging studies HD—284 participants TRACK-HD (100 control, 104 premanifest, 80 manifest) 159 PREDICT-HD (36 control 128...
Biomarkers of Huntington's disease (HD) in cerebrospinal fluid (CSF) could be value elucidating the biology this genetic neurodegenerative disease, as well development novel therapeutics. Deranged synaptic and immune function have been reported HD, concentrations protein neurogranin microglial TREM2 are increased other diseases. We therefore used ELISAs to quantify CSF samples from HD mutation carriers controls. concentration was not significantly altered compared controls, nor it associated...
The identification of sensitive biomarkers is essential to validate therapeutics for Huntington disease (HD). We directly compare structural imaging markers across the largest collective HD dataset identify a set robust multicenter variation and derive upper estimates on sample sizes clinical trials in HD.We used 1 postprocessing pipeline retrospectively analyze T1-weighted magnetic resonance (MRI) scans from 624 participants at 3 time points, PREDICT-HD, TRACK-HD, IMAGE-HD studies. mixed...
Investigating early white matter (WM) change in Huntington's disease (HD) can improve our understanding of the way which spreads from striatum.
Abstract Brain-derived neurotrophic factor (BDNF) is implicated in the survival of striatal neurons. BDNF function reduced Huntington’s disease (HD), possibly because mutant huntingtin impairs its cortico-striatal transport, contributing to neurodegeneration. The trophic pathway a therapeutic target, and blood has been suggested as potential biomarker for HD, but not quantified cerebrospinal fluid (CSF) HD. We CSF plasma HD-CSF cohort (20 pre-manifest 40 manifest HD mutation carriers 20 age...
An unresolved goal in face perception is to identify brain areas involved processing and simultaneously understand the timing of their involvement. Currently, high spatial resolution imaging techniques fusiform gyrus as subserving invariant features relating identity. High temporal localize an early latency evoked component-the N/M170-as having a major generator region; however, this component not believed be associated with To resolve this, we used novel magnetoencephalographic beamformer...
Abstract Structural connectomes derived using diffusion tractography are increasingly used to investigate white matter connectivity in neurological diseases. However inherent biases algorithms may lead both false negatives and positives connectome construction. A range of graph thresholding approaches more recently several streamline filtering have been developed address these issues. there is no consensus the literature regarding best available approach. Using a cohort Huntington’s disease...
Proton magnetic resonance spectroscopy is a non-invasive method of exploring cerebral metabolism. In Huntington's disease, altered proton spectroscopy-determined concentrations several metabolites have been described; however, findings are often discrepant and longitudinal studies lacking. may represent source biomarkers, thus their relationship with established markers disease progression require further exploration to assess prognostic value elucidate pathways associated neurodegeneration....