A5060138406- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Neurological Disease Mechanisms and Treatments
- Neurological Disorders and Treatments
- Sphingolipid Metabolism and Signaling
- Cerebrovascular and genetic disorders
- Parkinson's Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Metabolomics and Mass Spectrometry Studies
- S100 Proteins and Annexins
- Pharmacological Effects and Toxicity Studies
- Erythrocyte Function and Pathophysiology
- Cerebrovascular and Carotid Artery Diseases
- Bone and Dental Protein Studies
- Nuclear Receptors and Signaling
- Fungal Biology and Applications
- Lipid Membrane Structure and Behavior
- Atrial Fibrillation Management and Outcomes
- Metabolism and Genetic Disorders
- Pregnancy and preeclampsia studies
- Multiple Sclerosis Research Studies
- Medicinal Plants and Bioactive Compounds
- Health, Environment, Cognitive Aging
- Ginkgo biloba and Cashew Applications
- Mitochondrial Function and Pathology
National University of Singapore
2014-2025
National University Health System
2018-2025
University Health System
2023-2025
King's College London
2023-2024
Harvard University
2019
Massachusetts General Hospital
2019
Amsterdam Neuroscience
2019
University of Arizona
2015
Abstract INTRODUCTION Using an Asian cohort with high prevalence of concomitant cerebrovascular disease (CeVD), we evaluated the performance a plasma immunoassay for tau phosphorylated at threonine 217 (p‐tau217) in detecting amyloid beta positivity (Aβ+) on positron emission tomography and cognitive decline, based three‐range reference, which stratified patients into low‐, intermediate‐, high‐risk groups Aβ+. METHODS Brain status (Aβ– [ n = 142] vs Aβ+ 73]) PET scans was assessed along...
Cerebrovascular disease (CeVD) and neurodegenerative dementia such as Alzheimer's (AD) are frequently associated comorbidities in the elderly, sharing common risk factors pathophysiological mechanisms including neuroinflammation. Osteopontin (OPN) is an inflammatory marker found upregulated vascular diseases well AD. However, its involvement (VaD) pre-dementia stages, namely cognitive impairment no (CIND), both of which fall under spectrum (VCI), has yet to be examined. Its correlations with...
Abstract Introduction There is increasing evidence that phosphorylated tau (P‐tau181) a specific biomarker for Alzheimer's disease (AD) pathology, but its potential utility in non‐White patient cohorts and patients with concomitant cerebrovascular (CeVD) unknown. Methods Single molecule array (Simoa) measurements of plasma P‐tau181, total tau, amyloid beta (Aβ)40 Aβ42, as well derived ratios were correlated neuroimaging modalities indicating brain (Aβ+), hippocampal atrophy, CeVD...
Low blood concentrations of the diet-derived compound ergothioneine (ET) have been associated with cognitive impairment and cerebrovascular disease (CeVD) in cross-sectional studies, but it is unclear whether ET levels can predict subsequent functional decline. Here, we examined temporal relationships between plasma status cognition a cohort 470 elderly subjects attending memory clinics Singapore. All participants underwent baseline measurements as well neuroimaging for CeVD brain atrophy....
Abstract Introduction Plasma neurofilament light chain (NfL) is a potential biomarker for neurodegeneration in Alzheimer's disease (AD), ischemic stroke, and non‐dementia cohorts with cerebral small vessel (CSVD). However, studies of AD populations high prevalence concomitant CSVD to evaluate associations brain atrophy, CSVD, amyloid beta (Aβ) burden on plasma NfL are lacking. Methods Associations were tested between Aβ, medial temporal lobe atrophy (MTA) as well neuroimaging features...
Alzheimer's disease (AD) is characterized by accumulation of β-amyloid plaques (AP) and neurofibrillary tangles (NFT) in the cortex, together with synaptic loss amyloid angiopathy. Perturbations brain lysosomal system, including cathepsin family proteases, have been implicated AD where they may be involved proteolytic clearance misfolded abnormally aggregated peptides. However, status D (catD) unclear Lewy body dementia, second most common form neurodegenerative dementia after AD, bodies...
Chronically dysregulated neuroinflammation has been implicated in neurodegenerative dementias, with separate studies reporting increased brain levels of inflammatory mediators and gliosis Alzheimer's disease (AD) as well Lewy body dementias (LBD). However, it is unclear whether the nature extent neuroinflammatory responses LBD are comparable to those AD. In this study, we performed head-to-head measurements a panel cytokines post-mortem neocortex AD versus two major clinical subtypes LBD,...
Concomitant cerebrovascular diseases (CeVD) have been identified as an important determinant of Alzheimer's disease (AD) progression. Development robust blood-based biomarkers will provide critical tools to evaluate prognosis and potential interventional strategies for AD with CeVD.
While elevated blood glial fibrillary acidic protein (GFAP) has been associated with brain amyloid pathology, whether this association occurs in populations high cerebral small vessel disease (CSVD) concomitance remains unclear.
Tumor necrosis factor-receptor 1 (TNF-R1)-mediated signaling is critical to the regulation of inflammatory responses. TNF-R1 can be proteolytically released into systemic blood circulation in a soluble form (sTNF-R1), where it binds circulating TNF and functions attenuate TNF-mediated inflammation. Increases peripheral sTNF-R1 have been reported both Alzheimer's disease (AD) dementia vascular (VaD). However, status predementia subjects (cognitive impairment, no dementia, CIND) unknown,...
Abstract INTRODUCTION Cranial computed tomography (CT) is an affordable and widely available imaging modality that used to assess structural abnormalities, but not quantify neurodegeneration. Previously we developed a deep‐learning–based model produced accurate robust cranial CT tissue classification. MATERIALS AND METHODS We analyzed 917 744 magnetic resonance (MR) scans from the Gothenburg H70 Birth Cohort, 204 241 MR participants of Memory Clinic Singapore. tested associations between six...
Vascular dementia (VaD) is a leading cause of in the elderly together with Alzheimer's disease limited treatment options. Poor understanding pathophysiology underlying VaD hindering development new therapies. Hence, to unravel its molecular pathology, an iTRAQ-2D-LC-MS/MS strategy was used for quantitative analysis pooled lysates from Brodmann area 21 pathologically confirmed cases and matched non-neurological controls. A total 144 differentially expressed proteins out 2281 confidently...
Abstract Background There has been ongoing research impetus to uncover novel blood-based diagnostic and prognostic biomarkers for Alzheimer’s disease (AD), vascular dementia (VaD), related cerebrovascular (CEVD)-associated conditions within the spectrum of cognitive impairment (VCI). Sphingosine-1-phosphates (S1Ps) are signaling lipids which act on S1PR family cognate G-protein-coupled receptors have shown modulate neuroinflammation, a process known be involved in both neurodegenerative...
Abstract INTRODUCTION The prognostic utility of plasma proteomics for cognitive decline and dementia in a Southeast Asian population characterized by high cerebrovascular disease (CeVD) burden is underexplored. METHODS We examined this Singaporean memory clinic cohort 528 subjects ( n = 300, CeVD; 167, incident decline) followed‐up 4 years. RESULTS Of 1441 proteins surveyed, 12‐protein signature significantly predicted q ‐value < .05). Sixteen diverse biological processes were implicated...
Objective: The underlying mechanisms of mild behavioral impairment (MBI), a marker for cognitive and dementia, have remained unclear especially in multiethnic Asian population. study aimed to examine whether baseline Alzheimer disease biomarkers, including plasma neurofilament light (NfL) chain, phosphorylated tau-181 (p-tau181), the p-tau181-to-amyloid-β42 (p-tau181/Aβ42) ratio, could predict MBI incidence dementia-free older adults. Methods: Participants were recruited from community...
Background The relationship of left atrial ( LA ) strain with cognition in the absence fibrillation is poorly understood. We investigated association cognitive impairment and its pathogenetic subtype (vascular [ VCI ] or neurodegenerative) underlying mechanisms via associations circulating neuroimaging markers cerebrovascular disease. Methods Results (reservoir, conduit LAScd ], contractile) was determined using speckle‐tracking echocardiography a prospective memory clinic cohort brain...
In the brain, extracellular matrix (ECM) composition shapes neuronal microenvironment and can undergo substantial changes with cerebral pathology. Brevican is integral to formation of ECM’s neuroprotective perineuronal nets (PNNs). Decreased brevican levels were reported in vascular dementia (VaD) but not Alzheimer’s disease (AD). However, status clinical cohorts high concomitance AD pathological burden cerebrovascular (CeVD) unclear. this study, 32 non-cognitively impaired (NCI), 97...
Collapsin response mediator protein-2 (CRMP2) regulates axonal growth cone extension, and increased CRMP2 phosphorylation may lead to degeneration. Axonal synaptic pathology is an important feature of Lewy body dementias (LBD), but the state (pCRMP2) as well its correlations with markers neurodegeneration have not been studied in these dementias. Hence, we measured at Thr509, Thr514 Ser522, β-amyloid (Aβ), tau-phosphorylation, α-synuclein function postmortem neocortex a longitudinally...
Background:The translocase of the outer membrane (TOM) is a vital mitochondrial transport system facilitating importation nuclear encoded proteins into organelle. While dysfunction, including perturbation oxidative phosphorylation (OXPHOS) complex, evident in Alzheime r's disease (AD), it remains unclear whether observed OXPHOS deficits may be associated with TOM alterations. Objectives:To correlate subunits complex AD. Methods:Postmortem neocortex (BA40) from AD and age-matched controls...
Abstract Background Alzheimer’s disease (AD) and vascular dementia (VaD) are two of the commonest causes in elderly. Of myriad biomolecules implicated pathogenesis, sphingolipids have attracted relatively scant research attention despite their known involvement multiple pathophysiological processes. The potential utility peripheral as biomarkers cohorts with high concomitance cerebrovascular diseases is also unclear. Methods Using a lipidomics platform, we performed case–control study plasma...