A5038577973- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Cancer-related cognitive impairment studies
- Analytical Chemistry and Chromatography
- Receptor Mechanisms and Signaling
- Functional Brain Connectivity Studies
- Parkinson's Disease Mechanisms and Treatments
- Pharmacological Effects and Toxicity Studies
- Acute Myeloid Leukemia Research
- Computational Drug Discovery Methods
- Metabolomics and Mass Spectrometry Studies
- Advanced Proteomics Techniques and Applications
- Neuropeptides and Animal Physiology
- Health Systems, Economic Evaluations, Quality of Life
- S100 Proteins and Annexins
- Amyotrophic Lateral Sclerosis Research
- Neurological Disease Mechanisms and Treatments
- Identity, Memory, and Therapy
- Neuroscience and Neuropharmacology Research
- Bayesian Modeling and Causal Inference
- Bipolar Disorder and Treatment
- Cell Image Analysis Techniques
- Frailty in Older Adults
- Animal Behavior and Welfare Studies
- Statistical Methods in Clinical Trials
University of Wisconsin–Madison
2023-2025
Wellcome/MRC Cambridge Stem Cell Institute
2023
University of Cambridge
2023
University of Pittsburgh
2016-2020
Chevron (United States)
2018
George Mason University
2015
Importance Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 considered to have the most utility. However, availability of tests research and clinical use has been limited. Expanding access this highly accurate AD crucial wider evaluation implementation tests. Objective To determine utility novel commercially available immunoassay plasma detect pathology evaluate reference ranges abnormal amyloid β (Aβ) longitudinal change across 3...
Abstract INTRODUCTION Understanding longitudinal change in key plasma biomarkers will aid detecting presymptomatic Alzheimer's disease (AD). METHODS Serial samples from 424 Wisconsin Registry for Prevention participants were analyzed phosphorylated‐tau217 (p‐tau217; ALZpath) and other AD biomarkers, to study trajectories relation disease, health factors, cognitive decline. Of the participants, 18.6% with known amyloid status positive (A+); 97.2% cognitively unimpaired (CU). RESULTS In CU,...
Cerebrospinal fluid (CSF) dynamics are increasingly studied in aging and neurological disorders. Models of CSF-mediated waste clearance suggest that altered CSF could play a role the accumulation toxic CNS, with implications for Alzheimer's disease other proteinopathies. Therefore, approaches enable quantitative volumetric assessment flow velocities be value. In this study we demonstrate feasibility 4D MRI simultaneous throughout ventricular system, evaluate associations to arterial...
Capillary HPLC (cLC) with gradient elution is the separation method of choice for fields proteomics and metabolomics. This due to complementary nature cLC flow rates electrospray or nanospray ionization mass spectrometry (ESI-MS). The small column diameters result in good sensitivity. Good concentration sensitivity also possible by injection relatively large volumes solution relying on solvent-based solute focusing. However, if volume too solutes are poorly retained during injection,...
Abstract INTRODUCTION Patterns of signal from tau positron emission tomography (tau‐PET) confined to the medial temporal lobe (MTL) or extended into neocortex may be relevant for Alzheimer's disease (AD) research if they are linked differential biomarker levels and cognitive decline. METHODS Visual assessment Tau‐PET [F‐18]florquinitau (FQT) exams 728 initially non‐demented older adults yielded four uptake groups: tau‐negative (T−), MTL‐only (T+ MTL ), neocortex‐only Neo both MTL&Neo )....
Objective: Blood-based biomarkers are valued for their lower cost and less invasive nature, though issues with widespread implementation accessibility remain. Process-based scores from story recall have been shown to detect neuronal network disturbances typical of Alzheimer's disease (AD) pathology more effectively than traditional metrics. This study examined the associations between process-based concurrent plasma AD in older adults without dementia, while also comparing them Additionally,...
INTRODUCTION: This study uses longitudinal amyloid biomarker and cognitive data to generate sample size estimates for two-armed, pre-clinical clearance clinical trials. METHODS: PET PiB DVR ranges defined three groups (positive, "A+"; sub threshold/low positive, "subA+"; negative, "A-") in cognitively unimpaired Wisconsin Registry Alzheimer's Prevention participants. Amyloid group trajectories estimated from mixed effects models informed per-treatment-arm detect plausible treatment over...
Abstract INTRODUCTION Targeted proteomic assays may be useful for diagnosing and staging Alzheimer's disease related dementias (ADRD). We evaluated the performance of a 120‐marker central nervous system (CNS) NUcleic acid Linked Immuno‐Sandwich Assay (NULISA) panel in samples spanning (AD) spectrum. METHODS Cross‐sectional plasma ( n = 252) were analyzed using NULISAseq CNS from Alamar Biosciences. Receiver‐operating characteristic (ROC) analyses demonstrated accuracy NULISAseq‐tau...
Abstract INTRODUCTION Cognitively unimpaired (CU) amyloid beta (Aβ)+ individuals with elevated plasma glial fibrillary acidic protein (GFAP) have an increased risk of Alzheimer's disease (AD)‐related progression. We tested the utility GFAP for population enrichment CU populations in clinical trials. METHODS estimated longitudinal progression, effect size, and costs hypothetical trials designed to test 25% drug on reducing tau positron emission tomography (PET) accumulation medial temporal...
Abstract INTRODUCTION Multi‐etiology dementia necessitates in vivo markers of copathologies including misfolded ‐synuclein (syn). We measured syn aggregates (syn‐seeds) via qualitative seed amplification assays (synSAA) and examined relationships with Alzheimer's disease (AD). METHODS Cerebrospinal fluid (CSF) was obtained from 420 participants two AD risk cohorts (35% male; 91% cognitively unimpaired; mean [standard deviation] age, 65.42 [7.78] years; education, 16.17 [2.23]) years). synSAA...
Abstract INTRODUCTION Medical conditions prevalent in Black adults within the United States have been associated with plasma tau phosphorylated at threonine 217 (p‐tau217); however, insufficient p‐tau217 research has conducted adults. METHODS Participants included n = 233 predominantly cognitively unimpaired enrolled African Americans Fighting Alzheimer's Midlife study. Subsamples had creatinine ( 137) and positron emission tomography (PET; amyloid‐PET 65 [amyloid‐PET‐positive 16/65];...
We have developed a method for online collection and quantitation of neuropeptides in rat brain microdialysates using on-column dimethylation with capillary liquid chromatography-tandem mass spectrometry (cLC-MS2). This addresses number the challenges quantifying cLC-MS. It is also completely automated robust preparation stable isotope labeled-peptide internal standards to correct matrix effects thus ensure accurate quantitation. Originally tissue-derived proteomics samples (Raijmakers et...
Abstract INTRODUCTION Multi-etiology dementia necessitates in-vivo markers of copathologies including misfolded α -synuclein (syn). We measured syn aggregates (syn-seeds) via qualitative seed amplifcation assays (synSAA) and examined relationships with Alzheimer’s disease (AD). METHODS Cerebrospinal fluid (CSF) was obtained from 420 participants in two Wisconsin AD risk cohorts (35% male; 91% cognitively unimpaired; mean (SD) age, 65.42 (7.78) years; education, 16.17 (2.23) years). synSAA...
There are many processes that actively alter the concentrations of solutes in extracellular space. Enzymatic reactions, either by soluble enzymes or membrane-bound ectoenzymes, and uptake clearance two such processes. Investigations ectoenzymatic reactions vivo is challenging, particularly brain. Studies using microdialysis have revealed some qualitative information about what may be present, but a sampling technique so it not designed to control conditions as substrate concentration outside...
Abstract Background Previous studies have found connections between recall of proper names (PN) and amyloid positivity in cognitively unimpaired (CU) adults at risk for Alzheimer’s Disease (AD; Mueller et al., 2020). Given the promising prospect employing plasma‐based biomarkers to determine burden, we looked associations longitudinal change PN total score from Logical Memory (LM) story test plasma pTau217. Method Participants Wisconsin Registry Prevention (WRAP) study, who were CU baseline...
Structured Abstract INTRODUCTION Targeted proteomic assays may be useful for diagnosing and staging Alzheimer’s disease related dementias (ADRD). We evaluated the performance of a 120-marker central nervous system (CNS) NUcleic acid-Linked Immuno-Sandwich Assay (NULISA) panel in samples spanning AD spectrum. METHODS Cross-sectional plasma (n=252) were analyzed using Alamar’s NULISAseq CNS panel. ROC analyses demonstrated NULISAseq-pTau217 accuracy detecting amyloid (A) tau (T) PET...
Abstract Background TDP‐43 nuclear clearance and cytoplasmic aggregation occur in an estimated 30‐60% of cases Alzheimer’s disease (AD), but this pathology can currently only be established at autopsy. Nuclear leads to inclusion cryptic exons pre‐mRNA, some which are spliced in‐frame translated into proteins carrying novel exon‐encoded epitopes. We developed a Meso Scale Discovery (MSD) ELISA against the TDP‐43‐associated neoepitope within HDGFL2 protein found significantly elevated levels...
Abstract Background Blood‐based AD biomarker tests will be essential clinical tools to provide accessible and affordable screening monitoring for disease‐modifying therapeutics (DMT) as well advancing overall care. Tau phosphorylated at position 217 (pTau217) is considered have the highest accuracy in identifying Alzheimer’s disease (AD) pathology using blood. We describe a multi‐cohort evaluation of Simoa ALZpath pTau217 assay plasma, including memory clinic patients, performance context...
Abstract Background Mobile phlebotomy is an attractive option for the study of Alzheimer’s disease (AD) in rural and underserved populations, but logistics collecting, shipping these samples outside clinical settings can introduce additional sources variability. Knowledge limited on impact field collection blood‐based biomarkers, especially protein stability when dry ice not available during shipping. Our looks into effects holding plasma under refrigeration prior to freezing AD biomarker...