A5069442898- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Metabolomics and Mass Spectrometry Studies
- Bioinformatics and Genomic Networks
- Computational Drug Discovery Methods
- Diet and metabolism studies
- Tryptophan and brain disorders
- Health, Environment, Cognitive Aging
- Mitochondrial Function and Pathology
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Clusterin in disease pathology
- Neurological Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Nutritional Studies and Diet
- Health Systems, Economic Evaluations, Quality of Life
- Frailty in Older Adults
- Parkinson's Disease Mechanisms and Treatments
- Cholesterol and Lipid Metabolism
- Advanced Proteomics Techniques and Applications
- Genetic Associations and Epidemiology
- S100 Proteins and Annexins
- Amyotrophic Lateral Sclerosis Research
- Advanced Neuroimaging Techniques and Applications
- Folate and B Vitamins Research
National Institute on Aging
2016-2025
National Institutes of Health
2016-2025
St George's, University of London
2024
University College London
2024
Institute on Aging
2010-2022
Karolinska Institutet
2022
National Institute on Drug Abuse
2012-2018
Johns Hopkins University
2010-2017
Johns Hopkins Medicine
2012-2017
Emory University
2001-2017
The restless legs syndrome (RLS) is a common neurologic disorder characterized by an irresistible urge to move the legs. It major cause of sleep disruption. Periodic limb movements in are detectable most patients with RLS and represent objective physiological metric.To search for sequence variants contributing RLS, we performed genomewide association study two replication studies. To minimize phenotypic heterogeneity, focused on who had objectively documented periodic sleep. We measured...
Alzheimer's disease is a common and devastating for which there no readily available biomarker to aid diagnosis or monitor progression. Biomarkers have been sought in CSF but previous study has used two-dimensional gel electrophoresis coupled with mass spectrometry seek biomarkers peripheral tissue. We performed case–control of plasma using this proteomics approach identify proteins that differ the state relative aged controls. For discovery-phase analysis, 50 people dementia were recruited...
Abstract Introduction It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Methods Within the autopsy cohort of Baltimore Longitudinal Study Aging, we measured concentration and assessed ratios glycolytic amino acids, serine, glycine, alanine to glucose. We also quantified protein levels neuronal (GLUT3) astrocytic (GLUT1) transporters. Finally, relationships between plasma before death tissue Results Higher...
Abstract Introduction The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, nonprofit organizations to develop new research directions transform our understanding disease (AD) propel the development critically needed therapies. In response their recommendations, big data at multiple levels are being generated integrated study network failures in disease. We used metabolomics as a global biochemical approach identify peripheral metabolic...
Background The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism AD pathogenesis are unclear. Understanding how global perturbations related to severity neuropathology eventual expression symptoms at-risk individuals critical developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses both brain blood identify correlates their associations with prodromal...
<h3>Context</h3> Blood-based analytes may be indicators of pathological processes in Alzheimer disease (AD). <h3>Objective</h3> To identify plasma proteins associated with AD pathology using a combined proteomic and neuroimaging approach. <h3>Design</h3> Discovery-phase proteomics to correlates pathology. Confirmation validation immunodetection replication set an animal model. <h3>Setting</h3> A multicenter European study (AddNeuroMed) the Baltimore Longitudinal Study Aging....
Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as marker of 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) the Swedish BioFINDER study 1,464). Plasma was significantly increased all cortical amyotrophic lateral sclerosis atypical parkinsonian disorders. We...
Abstract Introduction Rapid growth of the older adult population requires greater epidemiologic characterization dementia. We developed national prevalence estimates diagnosed dementia and subtypes in highest risk United States (US) population. Methods analyzed Centers for Medicare & Medicaid administrative enrollment claims data 100% fee‐for‐service beneficiaries enrolled during 2011–2013 age ≥68 years as December 31, 2013 (n = 21.6 million). Results Over 3.1 million (14.4%) had a claim...
Background The metabolic basis of Alzheimer disease (AD) pathology and expression AD symptoms is poorly understood. Omega-3 -6 fatty acids have previously been linked to both protective pathogenic effects in AD. However, date little known about how the abundance these species affected by differing levels brain. Methods findings We performed profiling on brain tissue samples from 43 individuals ranging age 57 95 y old who were stratified into three groups: (N = 14), controls 14) "asymptomatic...
The strongest genetic risk factor for Alzheimer disease (AD), the apolipoprotein E (APOE) gene, has a stronger association among women compared with men. Yet limited work evaluated between APOE alleles and markers of AD neuropathology in sex-specific manner.
The complicated cellular and biochemical changes that occur in brain during Alzheimer's disease are poorly understood. In a previous study we used an unbiased label-free quantitative mass spectrometry-based proteomic approach to analyze these at systems level post-mortem cortical tissue from patients with (AD), asymptomatic (AsymAD), controls. We found modules of co-expressed proteins correlated AD phenotypes, some which were enriched identified as risk factors for by genetic studies. amount...
Understanding longitudinal plasma biomarker trajectories relative to brain amyloid changes can help devise Alzheimer's progression assessment strategies.
Abstract Blood phosphorylated tau (p-tau) biomarkers, including p-tau217, show high associations with Alzheimer’s disease (AD) neuropathologic change and clinical stage. Certain plasma p-tau217 assays recognize forms additionally at threonine-212, but the contribution of p-tau212 alone to AD is unknown. We developed a blood-based immunoassay that specific without cross-reactivity p-tau217. Here, we examined diagnostic utility p-tau212. In five cohorts ( n = 388 participants), showed...
<b>Objective: </b> To describe the incidence and characteristics of acute rapidly progressive visual loss in idiopathic intracranial hypertension (IIH). <b>Methods: We reviewed medical records all patients with IIH seen at two institutions. “Fulminant IIH” was defined as onset symptoms signs (less than 4 weeks between initial severe loss), rapid worsening over a few days, normal brain MRI MR venography (or CT venogram). <b>Results: Sixteen cases “fulminant were included (16 women, mean age...
To study differences in longitudinal changes regional cerebral blood flow (rCBF) between apolipoprotein E (APOE) epsilon4 carriers and noncarriers nondemented older adults from the Baltimore Longitudinal Study of Aging using positron emission tomography order to determine whether there are regionally specific rCBF APOE that might be related its well-established role as a genetic risk factor for Alzheimer disease.Using oxygen 15 ([(15)O])-labeled water voxel-based analysis, we compared over...
Recently, quantitative metabolomics identified a panel of 10 plasma lipids that were highly predictive conversion to Alzheimer's disease (AD) in cognitively normal older individuals (n = 28, area under the curve [AUC] 0.92, sensitivity/specificity 90%/90%).Quantitative targeted serum using an identical method as index study.We failed replicate these findings substantially larger study from two independent cohorts-the Baltimore Longitudinal Study Aging ([BLSA], n 93, AUC 0.642, 51.6%/65.7%)...