A5103122755- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Metabolomics and Mass Spectrometry Studies
- Computational Drug Discovery Methods
- Radiopharmaceutical Chemistry and Applications
- Cholinesterase and Neurodegenerative Diseases
- S100 Proteins and Annexins
- Neurological Disease Mechanisms and Treatments
- Pharmacological Effects and Toxicity Studies
- Radiomics and Machine Learning in Medical Imaging
- Statistical Methods in Clinical Trials
- Cell Adhesion Molecules Research
- Genetic Associations and Epidemiology
- Analytical Methods in Pharmaceuticals
- Genomics and Rare Diseases
- Diabetes Treatment and Management
- Advanced Proteomics Techniques and Applications
- Medical Imaging Techniques and Applications
University of Pittsburgh
2024-2025
Children's Hospital of Pittsburgh
2024
Universidad de Granada
2024
Patients with Alzheimer's disease (AD) little or no quantifiable insoluble brain tau neurofibrillary tangle (NFT) pathology demonstrate stronger clinical benefits of therapies than those advanced NFTs. The formation NFTs can be prevented by targeting the intermediate soluble assemblies (STAs). However, biochemical understanding and biomarkers STAs are lacking. We show that Tris-buffered saline-soluble aggregates from autopsy-verified AD tissues include core sequence ~tau258-368. In...
Abstract The reliability of plasma biomarkers Alzheimer's disease (AD) can be compromised by protease‐induced degradation. This limit the feasibility conducting biomarker studies in environments that lack capacity for immediate processing and appropriate storage blood samples. We hypothesized collection tube supplementation with protease inhibitors improve stability at room temperatures (RT). In this study, we conducted a comparative analysis traditional ethylenediaminetetraacetic acid...
<title>Abstract</title> High-performance, resource-efficient methods for plasma amyloid-β (Aβ) quantification in Alzheimer’s disease are lacking; existing mass spectrometry-based assays resource- and time-intensive. We developed a streamlined spectrometry method with single immunoprecipitation step, an optimized buffer system, ≤75% less antibody requirement. Analytical clinical performances were compared in-house reproduced version of well-known two-step assay. The assay showed high dilution...
Phosphorylated tau (p-tau) 217 is a promising blood biomarker for Alzheimer's disease (AD). However, most p-tau217 assays have been validated solely in ethylenediaminetetraacetic acid (EDTA) plasma, leaving the clinical applicability of serum largely unexplored despite being preferred matrix many laboratories. To address this gap, we compared concentrations and diagnostic performances matched plasma samples using four research-use-only assays, including three from commercial sources i.e.,...
Abstract Background Neurofibrillary tangles (NFT), consisting of hyperphosphorylated tau aggregates, are one the major pathological hallmarks Alzheimer’s disease (AD). The burden NFTs correlates with cognitive decline, and in vivo detection NFT may help predict clinical progression AD. Mass spectrometry‐based proteomic analysis brain regions affected by holds potential to unveil molecular mechanisms underlying pathogenesis uncover novel diagnostic/prognostic biomarkers therapeutic targets....
Abstract Background Alzheimer’s disease (AD) is a multifaceted condition associated with various brain pathologies, necessitating diverse biomarkers for precise prognosis, diagnosis, clinical management, and therapeutic development/evaluation. The integration of multiple into single test can enhance efficiency, reduce analytical errors, save on specimen volume. Alamar Biosciences recently introduced the NULISAseq CNS panel, multiplex NUcleic acid‐linked Immuno‐Sandwich Assay (NULISA)...
Abstract Background Plasma phospho‐tau217 (p‐tau217) is a promising blood‐based biomarkers for Alzheimer's disease (AD). However, the accessibility of pTau217 tests both research and clinical applications has been constrained. Previous studies focused on highly‐phenotyped cohorts that differ substantially from wider population. To broaden access to this highly precise biomarker AD, we developed novel immunoassay p‐tau217 at University Pittsburgh (Pitt‐p‐tau217). Following thorough analytical...
Abstract Background Plasma p‐tau217 is probably the best‐performing blood biomarker to detect brain amyloid‐beta (Aβ) accumulation. However, previous studies were mostly performed in highly selected cohorts. Thus, it unclear if can be used independently of confirmatory neuroimaging tests identify individuals with abnormal Ab load wider population where positron emission tomography (PET) may unavailable. We evaluated feasibility plasma replacing PET two population‐based Methods This study...
Abstract Background Specific PSEN1 mutations cause early‐onset AD but their effects on blood biomarker levels are unknown. We evaluated autopsy‐confirmed individuals affected by six different mutations; two of known (L381V, C410Y) and three (A426P/E318G, M233L, V261I) unknown pathogenic status. The sixth patient had Autosomal Dominant (ADAD) not yet genotyped. Neuropathologically diagnosed sporadic (sAD; n=8) unaffected controls (n=7) were included for comparison. Method participants, except...
Abstract Background Amyloid β (Aβ) deposition in the brain is a pathological hallmark of Alzheimer's disease (AD). While immunoprecipitation‐mass spectrometry (IP‐MS) stands out as an accurate method for quantifying blood‐based Aβ peptides, its major limitations such prolonged sample preparation, extensive analysis time, large specimen volume, and high costs, present opportunities improvement. Consequently, we aimed to develop novel plasma IP‐MS assay that employs simplified significantly...
Abstract Background Plasma p‐tau217 is a highly promising biomarker for detecting Alzheimer’s disease (AD) pathology. However, it unclear how assays from different sources perform compared to one another. Moreover, studies in diverse cohorts and population‐based settings are limited. We performed direct comparison of four detect brain amyloid‐beta (Aβ) deposition or cognitive decline. Method included n=427 participants three separate southwestern Pennsylvania, USA. Cohort‐1 was the...