A5002116784- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Amyotrophic Lateral Sclerosis Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Parkinson's Disease Mechanisms and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Hereditary Neurological Disorders
- RNA regulation and disease
- Neurogenetic and Muscular Disorders Research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Neurological Disease Mechanisms and Treatments
- Bioinformatics and Genomic Networks
- Intracerebral and Subarachnoid Hemorrhage Research
- Health, Environment, Cognitive Aging
- Peripheral Nerve Disorders
- Cerebrovascular and genetic disorders
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Inflammation biomarkers and pathways
- Peripheral Neuropathies and Disorders
- Endoplasmic Reticulum Stress and Disease
- Gene expression and cancer classification
- Medicinal Plants and Neuroprotection
University College London
2016-2025
UK Dementia Research Institute
2018-2025
National Hospital for Neurology and Neurosurgery
2018-2022
China Medical University Hospital
2019
Queen Mary University of London
2019
China Medical University
2019
Sahlgrenska University Hospital
2019
University of Padua
2019
Basildon Hospital
2019
University of Oxford
2019
There are few validated fluid biomarkers in frontotemporal dementia (FTD). Glial fibrillary acidic protein (GFAP) is a measure of astrogliosis, known pathological process FTD, but has yet to be explored as potential biomarker.Plasma GFAP and neurofilament light chain (NfL) concentration were measured 469 individuals enrolled the Genetic FTD Initiative: 114 C9orf72 expansion carriers (74 presymptomatic, 40 symptomatic), 119 GRN mutation (88 31 53 MAPT (34 19 symptomatic) 183 non-carrier...
Cerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer's disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal (FTD), is less well established. We aimed determine the diagnostic an extended panel CSF differentiate range other dementias. immunoassays measure conventional markers amyloid and tau pathology (amyloid beta (Aβ)1–42, total (T-tau),...
We tested the hypothesis that plasma neurofilament light chain (NfL) identifies asymptomatic carriers of familial frontotemporal lobar degeneration (FTLD)-causing mutations at risk disease progression.Baseline NfL concentrations were measured with single-molecule array in original (n = 277) and validation 297) cohorts. C9orf72, GRN, MAPT mutation noncarriers from same families classified by severity (asymptomatic, prodromal, full phenotype) using CDR Dementia Staging Instrument plus behavior...
Abstract The abnormal assembly of tau protein in neurons is a pathological hallmark multiple neurodegenerative diseases, including Alzheimer’s disease (AD). Assembled associates with extracellular vesicles (EVs) the central nervous system individuals AD, which linked to its clearance and prion-like propagation. However, identities assembled species EVs, as well how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography single-particle...
Biomarkers that can track disease onset and progression in autosomal dominant Alzheimer's (ADAD) are needed. We investigate whether serum neurofilament light (NfL) concentration is associated with clinical cerebrospinal fluid (CSF) markers ADAD. also evaluate NfL differences between groups. Serum was measured cross-sectionally 60 individuals from ADAD families using an ultrasensitive immunoassay on the Single molecule array (Simoa) platform longitudinally exploratory study a subset of six...
Abstract Hereditary transthyretin amyloidosis (ATTRm) causes a disabling peripheral neuropathy as part of multisystem disorder. The recent development highly effective gene silencing therapies has highlighted the need for biomarkers disease activity to guide decision when start and stop treatment. In this study, we measured plasma neurofilament light chain (pNfL) concentration in 73 patients with ATTR found that pNfL was significantly raised ATTRm compared healthy controls. Furthermore, pNFL...
Objective To identify disease‐causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods We performed genome‐wide sequencing, homozygosity mapping, segregation analysis for novel gene discovery. used circular dichroism to show secondary structure changes isothermal titration calorimetry investigate the impact of on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays mass...
To determine whether blood biomarkers of neuronal damage (neurofilament light chain [NfL]), muscle (creatine kinase [CK]), and mass (creatinine) are altered in spinal bulbar muscular atrophy (SBMA) can be used as for disease severity.In this multicenter longitudinal prospective study, plasma serum were collected from 2 cohorts patients with SBMA London, United Kingdom (n = 50), Padova, Italy 43), along (amyotrophic lateral sclerosis [ALS]) healthy controls, levels NfL, CK, creatinine...
Background: There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA). Objective: To determine the profile of relevant to neurodegenerative disease CSF patients with CAA. Methods: We performed a detailed comparison markers, comparing CAA, Alzheimer’s (AD), and control (CS) participants, recruited from Biomarkers Outcomes CAA (BOCAA) study, Specialist Cognitive Disorders Service. Results: included 10 20 AD, CS participants (mean...
X-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to life-threatening inflammatory demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. AMN, found moderately elevated NfL with increased levels reflecting higher grading...
Reliable biomarkers of frontotemporal dementia (FTD) are currently lacking. FTD may be associated with chronic immune dysfunction, microglial activation and raised inflammatory markers, particularly in progranulin (GRN) mutation carriers. Levels soluble triggering receptor expressed on myeloid cells 2 (sTREM2) elevated Alzheimer's disease (AD), but they have not been fully explored FTD. We investigated whether cerebrospinal fluid (CSF) sTREM2 levels differ between controls, across different...
Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder presenting clinically with personality change (behavioural variant FTD (bvFTD)) or language deficits (primary progressive aphasia (PPA)). About third of familial mutations in GRN, MAPT and C9orf72 being the major genetic causes. Robust biomarkers underlying pathology are still lacking no markers currently able to distinguish those tau TDP-43 inclusions during life.This study used an ultrasensitive single molecule...
Increased CSF levels of a number synaptic markers have been reported in Alzheimer's disease (AD), but little is known about their concentrations frontotemporal dementia (FTD). We investigated this three proteins, neurogranin, SNAP-25, and synaptotagmin-1.CSF samples were analysed from 66 patients with disorder the FTD spectrum 19 healthy controls. Patients stratified by tau to Aβ42 ratio: those ratio > 1 considered as having likely AD pathology, i.e. an atypical form ('AD biomarker' group [n...
SUMMARY The abnormal assembly of tau protein in neurons is the pathological hallmark multiple neurodegenerative diseases, including Alzheimer’s disease (AD). In addition, assembled associates with extracellular vesicles (EVs) central nervous system patients AD, which linked to its clearance and prion-like propagation between neurons. However, identities species EVs, as well how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography...
<b><i>Background:</i></b> Chronic glial dysfunction may contribute to the pathogenesis of frontotemporal dementia (FTD). Cerebrospinal fluid (CSF) levels glia-derived proteins YKL-40 and chitotriosidase are increased in Alzheimer’s disease (AD) but have not been explored detail across spectrum FTD. <b><i>Methods:</i></b> We investigated whether CSF differed between FTD patients controls, different clinical genetic subtypes FTD, individuals with...
Abstract Mild traumatic brain injury is a relatively common event in contact sports and there increasing interest the long-term neurocognitive effects. The diagnosis largely relies on symptom reporting need for objective tools to aid prognosis. There are recent reports that blood biomarkers could potentially help triage patients with suspected normal CT findings. We have measured plasma concentrations of glial neuronal proteins explored their potential assessment mild sport. recruited...
Existing models of frontotemporal dementia (FTD) may not fully recapitulate the pathophysiology disease. To generate more pathophysiologically relevant FTD models, we engineered MAPT knockin mouse lines carrying triple mutations, among which MAPTP301S;Int10+3;S320F line exhibited robust tau pathology starting before 6 months age. Severe accumulation was predominantly observed in thalamus, hypothalamus, and amygdala with milder involvement cortex hippocampus, leading to synaptic loss, brain...
Background: Friedreich's ataxia (FRDA) is the most common autosomal recessive ataxia. Disease-modifying treatments are not available yet; however, several compounds currently under investigation. As a result, there growing need for identification of robust and easily accessible biomarkers monitoring disease activity therapeutic efficacy. The simultaneous measurement multiple brain-derived proteins could represent time- cost-efficient approach biomarker investigation in pathologically complex...
Frontotemporal dementia (FTD) is a heterogeneous group of neurodegenerative disorders with both sporadic and genetic forms. Mutations in the progranulin gene (GRN) are common cause FTD, causing either behavioural presentation or, less commonly, language impairment. Presence on T2-weighted images white matter hyperintensities (WMH) has been previously shown to be more commonly associated GRN mutations rather than other forms FTD. The aim current study was investigate longitudinal change WMH...
This study was undertaken to explore associations between plasma neurofilament light chain (pNfL) concentration (pg/ml) and disease activity in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) examine the usefulness of pNfL concentrations determining remission.
Frontotemporal dementia (FTD) is a pathologically heterogeneous neurodegenerative disorder associated usually with tau or TDP-43 pathology, although some phenotypes such as logopenic variant primary progressive aphasia are more commonly Alzheimer's disease pathology. Currently, there no biomarkers able to diagnose the underlying pathology during life. In this study, we aimed investigate potential of novel species within cerebrospinal fluid (CSF) for in FTD.
Abstract Introduction We tested the hypothesis that amyloid β (Aβ) peptide ratios are more stable than Aβ 42 alone when biofluids exposed to two preanalytical conditions known modify measurable concentration. Methods Human cerebrospinal fluid (CSF) and culture media (CM) from human cortical neurons were a series of volumes polypropylene surfaces. , 40 38 concentrations measured using multiplexed electrochemiluminescence immunoassay. Data analyzed mixed models in R. Results Decrease was...
Outcomes are unpredictable for neurological presentations of Wilson's disease (WD). Dosing regimens chelation therapy vary and monitoring depends on copper indices, which do not reflect end-organ damage.To identify a biomarker involvement in WD.Neuronal glial-specific proteins were measured plasma samples from 40 patients 38 age-matched controls. Patients divided into or hepatic those with recent deterioration associated non-adherence subcategorized as having active disease. Unified WD...
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...