A5041639072- Dementia and Cognitive Impairment Research
- Alzheimer's disease research and treatments
- Health, Environment, Cognitive Aging
- Advanced Neuroimaging Techniques and Applications
- Functional Brain Connectivity Studies
- Cardiovascular Health and Disease Prevention
- Advanced MRI Techniques and Applications
- Health disparities and outcomes
- Frailty in Older Adults
- S100 Proteins and Annexins
- Traumatic Brain Injury and Neurovascular Disturbances
- Health Systems, Economic Evaluations, Quality of Life
- MRI in cancer diagnosis
- Hearing Loss and Rehabilitation
- Neuroinflammation and Neurodegeneration Mechanisms
- Infective Endocarditis Diagnosis and Management
- Birth, Development, and Health
- Physical Activity and Health
- Intracerebral and Subarachnoid Hemorrhage Research
- Amyotrophic Lateral Sclerosis Research
- Noise Effects and Management
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Prion Diseases and Protein Misfolding
- Peripheral Neuropathies and Disorders
- Traumatic Brain Injury Research
National Hospital for Neurology and Neurosurgery
2015-2025
UK Dementia Research Institute
2018-2025
University College London
2015-2025
King's College London
2019-2022
MRC Unit for Lifelong Health and Ageing
2019-2022
London School of Hygiene & Tropical Medicine
2019-2022
Imperial College London
2022
Royal London Hospital
2022
Nia Association
2022
ID Genomics (United States)
2022
BackgroundMidlife hypertension confers increased risk for cognitive impairment in late life. The sensitive period exposure and extent that is mediated through amyloid or vascular-related mechanisms are poorly understood. We aimed to identify if, when, blood pressure change during adulthood were associated with late-life brain structure, pathology, cognition.MethodsParticipants from Insight 46, a neuroscience substudy of the ongoing longitudinal Medical Research Council National Survey Health...
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),...
The tau protein plays a central role in Alzheimer's disease (AD), and there is huge interest measuring blood cerebrospinal fluid (CSF).We developed set of immunoassays to measure specimens from humans diagnosed based on current best clinical CSF biomarker criteria.In CSF, mid-region- N-terminal-detected predominated rose disease. In plasma, an N-terminal assay (NT1) detected elevated levels AD AD-mild cognitive impairment (MCI). Plasma NT1 measurements separated controls AD-MCI (area under...
Alzheimer's disease has a preclinical stage when cerebral amyloid-b deposition occurs before symptoms emerge, and amyloid-b-targeted therapies may have maximum benefits.Existing status measurement techniques, including amyloid PET CSF testing, are difficult to deploy at scale, so blood biomarkers increasingly considered for screening.We compared three different blood-based techniques-liquid chromatography-mass spectrometry measures of plasma amyloid-b, single molecule array (Simoa)...
Midlife vascular risk burden is associated with late-life dementia. Less known about if and how exposure in early adulthood influences brain health.To determine the associations between adulthood, midlife, late life structure pathology using measures of white matter-hyperintensity volume, β-amyloid load, whole-brain hippocampal volumes.This prospective longitudinal cohort study, Insight 46, part Medical Research Council National Survey Health Development, which commenced 1946. Participants...
In pre-clinical Alzheimer’s disease, cerebral amyloid-β (Aβ) deposition precedes symptoms; Aβ-targeted therapies may have maximum benefits at this stage. Existing Aβ status measurement techniques, including amyloid PET and CSF testing, are difficult to upscale. We therefore compared the concordance of three different blood-based techniques (liquid chromatography-mass spectrometry (LC¬-MS) measures plasma Aβ, single molecule array (Simoa) phospho-tau181 (p-tau181)) with PET-positivity in...
The Alzheimer's Association Global Biomarker Standardization Consortium conducted a blinded case-control study to learn which phosphorylated tau (p-tau) assays provide the largest fold-changes in disease (AD) versus non-AD and show commutability measuring patient samples candidate certified reference materials (CRMs). Thirty-three different p-tau measured paired plasma cerebrospinal fluid (CSF) from 40 participants (25 with "AD pathology" 15 "non-AD by CSF amyloid beta [Aβ]42/Aβ40 p-tau181...
Freeze-thaw instability may contribute to preanalytical variation in blood-based biomarker studies. We investigated the effects of up four freeze-thaw cycles on single molecule array immunoassays serum neurofilament light chain and plasma total tau, amyloid β 1-40 (Aß40), Aβ 1-42 (Aβ42).Individuals who had peripheral venepuncture during investigation suspected neurodegenerative disease were recruited. After standardized preprocessing, 200 μL aliquots stored at -80°C within 60 minutes....
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...
Abstract Preliminary pathological and biomarker data suggest that SARS-CoV-2 infection can damage the nervous system. To understand what, where how occurs, we collected serum CSF from patients with COVID-19 characterized neurological syndromes involving PNS CNS (n = 34). We measured biomarkers of neuronal neuroinflammation, compared these non-neurological control groups, which included 94) without 24) COVID-19. detected increased concentrations neurofilament light, a dynamic damage, in those...
Abstract Introduction The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting results may differ, which can lead misunderstandings raises questions about commutability tests. Methods We obtained description (pre‐)analytical protocols sample reports 40 centers worldwide. A consensus approach allowed us propose harmonized comments...
A neuroimaging-based biomarker termed the brain age is thought to reflect variability in brain's ageing process and predict longevity. Using Insight 46, a unique narrow-age birth cohort, we aimed examine potential drivers correlates of age.
Abstract Human prion diseases are remarkable for long incubation times followed typically by rapid clinical decline. Seed amplification assays and neurodegeneration biofluid biomarkers remarkably useful in the phase, but their potential to predict onset healthy people remains unclear. This is relevant not only design of preventive strategies those at-risk diseases, more broadly, because prion-like mechanisms thought underpin many neurodegenerative disorders. Here, we report accrual a...
BACKGROUND: Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimers disease (AD) pathology. Multiple p-tau biomarkers on several analytical platforms are poised clinical use. The Association Global Biomarker Standardisation Consortium plasma phospho-tau Round Robin study engaged assay developers in blinded case-control p-tau, aiming to learn which assays provide the largest fold-changes AD compared non-AD, have strongest relationship between and cerebrospinal fluid (CSF),...
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...
<h3>Objective</h3> To investigate predictors of performance on a range cognitive measures including the Preclinical Alzheimer Cognitive Composite (PACC) and test for associations between cognition dementia biomarkers in Insight 46, substudy Medical Research Council National Survey Health Development. <h3>Methods</h3> A total 502 individuals born same week 1946 underwent assessment at age 69–71 years, an adapted version PACC nonverbal reasoning. Performance was characterized with respect to...
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...
The goals of this work were to quantify the independent and interactive associations β-amyloid (Aβ) white matter hyperintensity volume (WMHV), a marker presumed cerebrovascular disease (CVD), with rates neurodegeneration examine contributions
ABSTRACT INTRODUCTION Recent advancements in immunological methods accurately quantify biofluid biomarkers for identifying Alzheimer’s pathology and neurodegeneration. Despite this progress, more biomarkers, ideally blood, are needed effective patient management disease monitoring (AD) other neurodegenerative proteinopathies. METHODS We employed the Nucleic Acid-Linked Immuno-Sandwich Assay (NULISA™) central nervous system (CNS) panel biomarker quantification plasma, serum cerebrospinal...
Identifying and recruiting people with early pre-symptomatic Alzheimer's disease to neuroimaging research studies is increasingly important. The extent which results of these can be generalised depends on the recruitment representativeness participants involved. We now report participation patterns from a neuroscience sub-study MRC National Survey Health Development, "Insight 46". This study aimed recruit 500 for extensive clinical neuropsychological testing, neuroimaging. investigate how...
<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 INTRODUCTION We assessed the concordance of cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau measured on fully automated Lumipulse platform with pre‐symptomatic Alzheimer's disease (AD) pathology positron emission tomography (PET). METHODS In 72 individuals from Insight 46 study, CSF Aβ40, Aβ42, total (t‐tau), phosphorylated at site 181 (p‐tau181) were using Lumipulse, INNOTEST, Meso Scale Discovery (MSD) assays inter‐platform Pearson correlations derived. Aβ42 measures adjusted...