A5022462599- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Functional Brain Connectivity Studies
- Bioinformatics and Genomic Networks
- Health, Environment, Cognitive Aging
- Advanced Neuroimaging Techniques and Applications
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Health Systems, Economic Evaluations, Quality of Life
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Statistical Methods in Clinical Trials
- Neurological Disease Mechanisms and Treatments
- Tryptophan and brain disorders
- Metabolomics and Mass Spectrometry Studies
- Parkinson's Disease Mechanisms and Treatments
- Intracerebral and Subarachnoid Hemorrhage Research
- Medical Imaging Techniques and Applications
- Mitochondrial Function and Pathology
- S100 Proteins and Annexins
- Amyotrophic Lateral Sclerosis Research
- Statistical Methods and Inference
- Frailty in Older Adults
- Computational Drug Discovery Methods
- Genomics and Rare Diseases
- Folate and B Vitamins Research
Washington University in St. Louis
2016-2025
Hope Center for Neurological Disorders
2016-2025
Prevent Alzheimer’s Disease 2020
2016-2024
Centre for Addiction and Mental Health
2024
Rice University
2024
Institute for Neurodegenerative Disorders
2021-2024
Brigham and Women's Hospital
2013-2024
University of Ulsan
2024
Asan Medical Center
2024
Dankook University
2024
The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the develops over many years. Autosomal dominant has a predictable age at onset provides an opportunity to determine sequence changes that culminate symptomatic disease.
The accumulation of soluble and insoluble aggregated amyloid-beta (Aβ) may initiate or potentiate pathologic processes in Alzheimer's disease. Lecanemab, a humanized IgG1 monoclonal antibody that binds with high affinity to Aβ protofibrils, is being tested persons early
Alzheimer’s disease is associated with reduced β-amyloid clearance from the brain
Amyloid-beta (Abeta) accumulation in the brain extracellular space is a hallmark of Alzheimer's disease. The factors regulating this process are only partly understood. Abeta aggregation concentration-dependent that likely responsive to changes interstitial fluid (ISF) levels Abeta. Using vivo microdialysis mice, we found amount ISF correlated with wakefulness. also significantly increased during acute sleep deprivation and orexin infusion, but decreased infusion dual receptor antagonist....
Human apoE4 increases the concentration of soluble Aβ in brain by impairing its clearance.
We examined whether plasma β-amyloid (Aβ)42/Aβ40, as measured by a high-precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF p-tau181/Aβ42 reference standards.
Decreased sleep and attenuation of circadian fluctuations in Aβ reflect amyloid-associated pathology Alzheimer’s disease.
Abstract Introduction Cerebrospinal fluid analysis and other measurements of amyloidosis, such as amyloid‐binding positron emission tomography studies, are limited by cost availability. There is a need for more practical amyloid β (Aβ) biomarker central nervous system deposition. Methods We adapted our previously reported stable isotope labeling kinetics protocol to analyze the turnover concentrations Aβ38, Aβ40, Aβ42 in human plasma. Results Aβ isoforms have half‐life approximately 3 hours...
White matter hyperintensities (WMHs) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression Alzheimer's disease (AD). These observations typically interpreted as evidence vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features AD. We examined the severity distribution in...
Longitudinal cerebrospinal fluid biomarker analyses reveal decreases in neuronal injury markers later stages of autosomal-dominant Alzheimer’s disease.
Significance Beta-amyloid plaque accumulation, glucose hypometabolism, and neuronal atrophy are hallmarks of Alzheimer’s disease. However, the regional ordering these biomarkers prior to dementia remains untested. In a cohort with disease mutations, we performed an integrated whole-brain analysis three major imaging techniques: amyloid PET, [ 18 F]fluro-deoxyglucose structural MRI. We found that most gray-matter structures plaques later have hypometabolism followed by atrophy. Critically,...
The pathological hallmark of Alzheimer disease is the senile plaque principally composed tightly aggregated amyloid-beta fibrils (fAbeta), which are thought to be resistant degradation and clearance. In this study, we explored whether proteases capable degrading soluble Abeta (sAbeta) could degrade fAbeta as well. We demonstrate that matrix metalloproteinase-9 (MMP-9) can ability not shared by other sAbeta-degrading enzymes examined, including endothelin-converting enzyme, insulin-degrading...
It has been postulated that the development of amyloid plaques in Alzheimer's disease (AD) may result from an imbalance between generation and clearance amyloid-β peptide (Aβ). Although familial AD appears to be caused by Aβ overproduction, sporadic (the most prevalent form) impairment clearance. Recent evidence suggests several proteases contribute degradation Aβ. Furthermore, astrocytes have recently implicated as a potential cellular mediator degradation. In this study, we examined...
Highly sensitive and specific plasma biomarkers for Alzheimer’s disease (AD) have the potential to improve diagnostic accuracy in clinic facilitate research studies including enrollment prevention treatment trials. We recently reported CSF tau hyperphosphorylation, especially on T217, is an accurate predictor of β-amyloidosis at asymptomatic symptomatic stages. In current study, we determine by mass spectrometry utility p-tau isoforms detect AD pathology investigate isoforms’ profile...
Blood-based tests for brain amyloid-β (Aβ) pathology are needed widespread implementation of Alzheimer disease (AD) biomarkers in clinical care and to facilitate patient screening monitoring treatment responses trials.To compare the performance plasma Aβ42/40 measured using 8 different Aβ assays when detecting abnormal status patients with early AD.This study included 182 cognitively unimpaired participants 104 mild cognitive impairment from BioFINDER cohort who were enrolled at 3 hospitals...
Abstract Objective Accumulation of amyloid‐β (Aβ) by overproduction or underclearance in the central nervous system (CNS) is hypothesized to be a necessary event pathogenesis Alzheimer's disease. However, previously, there has not been method determine drug effects on Aβ production clearance human CNS. The objective this study was γ‐secretase inhibitor Methods We utilized recently developed stable‐isotope labeling combined with cerebrospinal fluid sampling directly measure during treatment...