A5062204294- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Functional Brain Connectivity Studies
- Influenza Virus Research Studies
- Respiratory viral infections research
- Amyloidosis: Diagnosis, Treatment, Outcomes
- S100 Proteins and Annexins
- Neuroscience and Neuropharmacology Research
- Frailty in Older Adults
- Neuroinflammation and Neurodegeneration Mechanisms
- Medical Imaging Techniques and Applications
- Epilepsy research and treatment
- Neurological Disease Mechanisms and Treatments
- Nicotinic Acetylcholine Receptors Study
- RNA and protein synthesis mechanisms
- Pharmacological Effects and Toxicity Studies
- Prion Diseases and Protein Misfolding
- Radiomics and Machine Learning in Medical Imaging
- Receptor Mechanisms and Signaling
- Bioinformatics and Genomic Networks
- Angiogenesis and VEGF in Cancer
- Cellular transport and secretion
- Tryptophan and brain disorders
- Axon Guidance and Neuronal Signaling
- Cholinesterase and Neurodegenerative Diseases
Janssen (United States)
2016-2025
Johnson & Johnson (United States)
2024
Janssen (Belgium)
2017-2024
Johnson & Johnson (Israel)
2024
Alzheimer’s Disease Neuroimaging Initiative
2023
Union Bank of Switzerland
2023
University of California, San Diego
2006-2021
Pfizer (United States)
2009-2013
University of California, Los Angeles
2004
Abstract Cerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate performance CSF p-tau217 as a AD comparison to p-tau181. In Swedish BioFINDER cohort ( n = 194), shows stronger correlations with positron emission tomography (PET) tracer [ 18 F]flortaucipir, and more accurately identifies individuals abnormally increased F]flortaucipir retention....
Plasma phospho-tau (p-tau) species have emerged as the most promising blood-based biomarkers of Alzheimer's disease. Here, we performed a head-to-head comparison p-tau181, p-tau217 and p-tau231 measured using 10 assays to detect abnormal brain amyloid-β (Aβ) status predict future progression dementia. The study included 135 patients with baseline diagnosis mild cognitive impairment (mean age 72.4 years; 60.7% women) who were followed for an average 4.9 years. Seventy-one participants had...
Abstract An unresolved question for the understanding of Alzheimer’s disease (AD) pathophysiology is why a significant percentage amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological phosphorylation. Here, biomarker study across three cohorts ( n = 1,016), we tested whether astrocyte reactivity...
Importance The recent proliferation of phosphorylated tau (p-tau) biomarkers has raised questions about their preferential association with the hallmark pathologies Alzheimer disease (AD): amyloid-β plaques and neurofibrillary tangles. Objective To determine whether cerebrospinal fluid (CSF) plasma p-tau preferentially reflect cerebral β-amyloidosis or tangle aggregation measured positron emission tomography (PET). Design, Setting, Participants This was a cross-sectional study 2...
Abstract Introduction Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences. Methods In BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non‐AD cerebrospinal fluid (CSF) profile group, according their amyloid beta 42/ (Aβ42/p‐tau) ratio. We performed head‐to‐head comparison nine plasma and CSF determined accuracy discriminate...
Cost-effective strategies for identifying amyloid-β (Aβ) positivity in patients with cognitive impairment are urgently needed recent approvals of anti-Aβ immunotherapies Alzheimer's disease (AD). Blood biomarkers can accurately detect AD pathology, but it is unclear whether their incorporation into a full diagnostic workflow reduce the number confirmatory cerebrospinal fluid (CSF) or positron emission tomography (PET) tests while classifying patients. We evaluated two-step determining Aβ-PET...
Abstract INTRODUCTION Plasma biomarkers are promising tools for Alzheimer's disease (AD) diagnosis, but comparisons with more established needed. METHODS We assessed the diagnostic performance of p‐tau 181 , 217 and 231 in plasma CSF 174 individuals evaluated by dementia specialists amyloid‐PET tau‐PET. Receiver operating characteristic (ROC) analyses to identify tau‐PET positivity. RESULTS had lower dynamic ranges effect sizes compared p‐tau. (AUC = 76%) 82%) assessments performed inferior...
Abstract INTRODUCTION Blood tests have the potential to improve accuracy of Alzheimer's disease (AD) clinical diagnosis, which will enable greater access AD‐specific treatments. This study compared leading commercial blood for amyloid pathology and other AD‐related outcomes. METHODS Plasma samples from Disease Neuroimaging Initiative were assayed with AD C2N Diagnostics, Fujirebio ALZPath, Janssen, Roche Quanterix. Outcomes measures positron emission tomography (PET), tau PET, cortical...
Recent advances in disease-modifying treatments highlight the need for accurately identifying individuals early Alzheimer's disease (AD) stages and monitoring of treatment effects. Plasma measurements phosphorylated tau (p-tau) are a promising biomarker AD, but different assays show varying diagnostic prognostic accuracies. The objective this study was to determine clinical performance novel plasma p-tau217 (p-tau217) assay, p-tau217+Janssen, perform head-to-head comparison an established...
Abstract INTRODUCTION Phosphorylated tau (p‐tau) biomarkers have been recently proposed to represent brain amyloid‐β (Aβ) pathology. Here, we evaluated the plasma biomarkers' contribution beyond information provided by demographics (age and sex) identify Aβ pathologies in individuals segregated as cognitively unimpaired (CU) impaired (CI). METHODS We assessed 138 CU 87 CI with available p‐tau231, 217 + , 181, Aβ42/40, GFAP Aβ‐ tau‐PET. RESULTS In CU, only p‐tau231 p‐tau217 significantly...
Abstract Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer’s disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance unclear. We compared key plasma tests using cross-sectional and longitudinal measures amyloid-β (Aβ)-PET, tau-PET, cognition as outcomes, benchmarked them against cerebrospinal fluid (CSF) tests. Samples from 998 individuals (mean[range] age 68.5[20.0-92.5], 53%...
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...
Background The recent emergence of a novel pandemic influenza A(H1N1) strain in humans exemplifies the rapid and unpredictable nature virus evolution need for effective therapeutics vaccines to control such outbreaks. However, resistance antivirals can be formidable problem as evidenced by currently widespread oseltamivir- adamantane-resistant seasonal A viruses (IFV). Additional antiviral approaches with mechanisms action are needed combat resistant strains. DAS181 (Fludase™) is sialidase...
Abstract Introduction Diagnosis of Alzheimer's disease (AD) based on amyloid beta (A), pathologic tau (T), and neurodegeneration (N) biomarkers in peripheral fluids promises to accelerate clinical trials intercept earlier. Methods Qualification a Simoa plasma p217+tau assay was performed, followed by utility evaluation cohort 227 subjects with broad A T spectrum. Results The accurate, precise, dilution linear, highly sensitive. All measured samples were within linear range the assay,...
Abstract INTRODUCTION Accumulating evidence indicates disproportionate tau burden and tau‐related clinical progression in females. However, sex differences plasma phosphorylated (p‐tau)217 prediction of subclinical cognitive brain changes are unknown. METHODS We measured baseline p‐tau217, glial fibrillary acidic protein (GFAP), neurofilament light (NfL) 163 participants (85 cognitively unimpaired [CU], 78 mild impairment [MCI]). In CU, linear mixed effects models examined biomarker...
We set out to identify tau PET-positive (A+T+) individuals among amyloid-beta (Aβ) positive participants using plasma biomarkers.
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),...
Importance Blood-based biomarkers for Alzheimer disease (AD) are clinically available, but their value is not well understood in syndromes typically associated with frontotemporal lobar degeneration (FTLD). Objective To investigate the clinical importance and detectability of AD FTLD-related neurodegenerative using 3 plasma biomarkers, phosphorylated tau 217 (p-tau217), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP). Design, Setting, Participants This...
Background. The first step in infection by human parainfluenza viruses (HPIVs) is binding to the surface of respiratory epithelial cells via interaction between viral receptor-binding molecules and sialic acid-containing receptors. DAS181, a recombinant sialidase protein containing catalytic domain Actinomyces viscosus sialidase, removes cell acid, we proposed that it would inhibit HPIV infection. Methods. Depletion acid receptors DAS181 was evaluated lectin-binding assays. Anti-HPIV...
Antiviral drug resistance for influenza therapies remains a concern due to the high prevalence of H1N1 2009 seasonal isolates which display H274Y associated oseltamivir-resistance. Furthermore, emergence novel raises potential that additional reassortments can occur, resulting in resistant virus. Thus, antiviral approaches are urgently needed. DAS181 (Fludase), sialidase fusion protein, has been shown have inhibitory activity against large number strains and highly pathogenic avian (HPAI)...
ABSTRACT DAS181 is a novel candidate therapeutic agent against influenza virus which functions via the mechanism of removing receptor, sialic acid (Sia), from adjacent glycan structures. and its analogues have previously been shown to be potently active multiple strains seasonal avian in several experimental models, including cell lines, mice, ferrets. Here we demonstrate that treatment leads desialylation both α2-6-linked α2-3-linked Sia ex vivo human lung tissue culture primary...
Background: Central nervous system-derived interleukin-1β plays a role in mood disorders. P2X7 receptor activation by adenosine-triphosphate leads to the release of interleukin-1β. Aims: This first-in-human study evaluated safety, tolerability, pharmacokinetics and pharmacodynamics novel central system-penetrant antagonist, JNJ-54175446, healthy participants. Methods: The had three parts: an ascending-dose fasted participants (0.5–300 mg JNJ-54175446); fed (50–600 mg); cerebrospinal fluid...
Endosomal secreted proteins can be detected in the CSF and inform on how Alzheimer’s defective trafficking pathway contribute to disease spread.