A5069275587- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Click Chemistry and Applications
- Medical Imaging Techniques and Applications
- Chemical Synthesis and Analysis
- Cell Adhesion Molecules Research
- Asymmetric Synthesis and Catalysis
- Computational Drug Discovery Methods
- Functional Brain Connectivity Studies
- Synthetic Organic Chemistry Methods
- S100 Proteins and Annexins
- Radiopharmaceutical Chemistry and Applications
- Innovative Microfluidic and Catalytic Techniques Innovation
- Monoclonal and Polyclonal Antibodies Research
- Cancer, Hypoxia, and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Oxidative Organic Chemistry Reactions
- Traditional and Medicinal Uses of Annonaceae
- Synthesis and Catalytic Reactions
- Asymmetric Hydrogenation and Catalysis
- Cancer Research and Treatments
- Glycosylation and Glycoproteins Research
- Cholinesterase and Neurodegenerative Diseases
- Peptidase Inhibition and Analysis
- Biochemical and Molecular Research
Janssen (United States)
2016-2025
Johnson & Johnson (United States)
2022-2025
University of Wisconsin–Madison
2025
Nobel Foundation
2025
Janssen (Belgium)
2017-2024
Enigma Diagnostics (United Kingdom)
2024
Johnson & Johnson (Israel)
2024
Alzheimer’s Disease Neuroimaging Initiative
2023
Union Bank of Switzerland
2023
Janssen (United Kingdom)
2021
Examination of nature's favorite molecules reveals a striking preference for making carbon–heteroatom bonds over carbon–carbon bonds—surely no surprise given that carbon dioxide is starting material and most reactions are performed in water. Nucleic acids, proteins, polysaccharides condensation polymers small subunits stitched together by bonds. Even the 35 or so building blocks from which these crucial made each contain, at most, six contiguous C−C bonds, except three aromatic amino acids....
Examination of nature's favorite molecules reveals a striking preference for making carbon–heteroatom bonds over carbon–carbon bonds—surely no surprise given that carbon dioxide is starting material and most reactions are performed in water. Nucleic acids, proteins, polysaccharides condensation polymers small subunits stitched together by bonds. Even the 35 or so building blocks from which these crucial made each contain, at most, six contiguous C−C bonds, except three aromatic amino acids....
Betrachtet man die in der Natur am häufigsten vorkommenden Verbindungen, so fällt auf, dass Bildung von Kohlenstoff-Heteroatom-Bindungen gegenüber Kohlenstoff-Kohlenstoff-Bindungen deutlich bevorzugt ist. Da zum einen Kohlendioxid Basisverbindung ist und andererseits das Medium natürlicher Reaktionen zumeist Wasser ist, überrascht dies sicherlich nicht. Nucleinsäuren, Proteine Polysaccharide sind polymere Kondensationsprodukte kleiner Untereinheiten, durch verknüpft sind. Sogar etwa 35...
Water, the medium of choice: Many reactions, such as Claisen rearrangements (see scheme), are dramatically accelerated when performed in aqueous suspension (“on water”) relative to organic solvents or even neat conditions. Low miscibility compounds with water is not detrimental: fact, it facilitates isolation products. Water a desirable solvent for chemical reactions reasons cost, safety, and environmental concerns, study has an intriguing history.1 Most notably, certain pericyclic...
Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to the degree cognitive impairment in Alzheimer's disease. We have recently reported early clinical results a novel PHF-tau targeting PET imaging agent, [F18]-T807. Since then, we investigated second [F18]-T808, with different pharmacokinetic characteristics, which may be favorable for disease and other tauopathies. Here, describe first human brain images [F18]-T808.
Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to the degree cognitive impairment in Alzheimer's disease. We have developed a novel PHF-tau targeting positron emission tomography imaging agent, [F-18]-
We wished to develop a highly selective positron emission tomography (PET) imaging agent targeting PHF-tau in human Alzheimer's disease (AD) brains.To screen potential tau binders, AD brain sections were used as source of native paired helical filament (PHF)-tau and Aβ rather than synthetic aggregates or fibrils generated vitro measure the affinity selectivity [(18)F]T807 Aβ. Brain uptake biodistribution mice also tested.In autoradiography results show that exhibits strong binding...
Twice poor equals potent: HIV-1 Protease assembles its own potent inhibitor through formation of the triazole linkage from azide- and alkyne-containing fragments that are themselves binders. Supporting information for this article is available on WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z502161_s.pdf or author. Please note: The publisher not responsible content functionality any supporting supplied by authors. Any queries (other than missing content) should be directed to...
Microreactor technology has shown potential for optimizing synthetic efficiency, particularly in preparing sensitive compounds. We achieved the synthesis of an [(18)F]fluoride-radiolabeled molecular imaging probe, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), integrated microfluidic device. Five sequential processes-[18F]fluoride concentration, water evaporation, radiofluorination, solvent exchange, and hydrolytic deprotection-proceeded with high radio-chemical yield purity shorter time...
The in situ click chemistry approach to lead discovery employs the biological target itself for assembling inhibitors from complementary building block reagents via irreversible connection chemistry. present publication discusses optimization of this target-guided strategy using acetylcholinesterase (AChE) as a test system. application liquid chromatography with mass spectroscopic detection selected ion mode product identification greatly enhanced sensitivity and reliability method. It...
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...
Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes with disease, experimental data demonstrated proliferation as a component of the neuropathology. In this study, we tested efficacy selective CSF1R inhibitor JNJ-40346527 (JNJ-527) P301S mouse tauopathy model. We first anti-proliferative effects JNJ-527 on microglia ME7 prion model, its impact inflammatory...
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...
Inflammation is associated with major depressive disorder (MDD). Translocator protein 18 kDa (TSPO), a putative biomarker of neuroinflammation, quantified using positron emission tomography (PET) and 11C-PBR28, TSPO tracer. We sought to (1) investigate binding in MDD subjects currently experiencing episode, (2) the effects antidepressants on binding, (3) determine relationship peripheral central inflammatory markers cerebral binding. Twenty-eight depressed (unmedicated (n = 12) or medicated...
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...
The target-guided, in situ click chemistry approach to lead discovery has been successfully employed for discovering acetylcholinesterase (AChE) inhibitors by incubating a selected enzyme/tacrine azide combination with variety of acetylene reagents that were not previously known interact the enzyme's peripheral binding site. triazole products, formed enzyme, identified HPLC-mass spectrometry analysis crude reaction mixtures. target-guided search was also successful when performed reagent...
Wasser, das Medium der Wahl: Viele Reaktionen, z. B. Claisen-Umlagerungen (siehe Schema), verlaufen in wässriger Suspension („an Wasser“) viel rascher als organischen Lösungsmitteln oder sogar Substanz. Die geringe Mischbarkeit organischer Verbindungen mit Wasser ist nicht von Nachteil; sie erleichtert vielmehr die Isolierung Produkte. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2005/z462883_s.pdf or from author. Please note:...