A5053990324- Alzheimer's disease research and treatments
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Medicinal Plants and Neuroprotection
- Neuroinflammation and Neurodegeneration Mechanisms
- Metabolomics and Mass Spectrometry Studies
- Parkinson's Disease Mechanisms and Treatments
- Advanced Proteomics Techniques and Applications
- Dendrimers and Hyperbranched Polymers
- RNA Interference and Gene Delivery
- Intracerebral and Subarachnoid Hemorrhage Research
- Neurological Disease Mechanisms and Treatments
- Synthesis and Characterization of Heterocyclic Compounds
Indiana University – Purdue University Indianapolis
2021-2024
Indiana University School of Medicine
2021-2024
Indiana University
2024
University School
2024
Abstract Tau aggregation is a defining histopathological feature of Alzheimer’s disease and other tauopathies. However, the cellular mechanisms involved in tau propagation remain unclear. Here, we performed an unbiased quantitative proteomic study to identify proteins that specifically interact with this seed. We identified Bassoon (BSN), presynaptic scaffolding protein, as interactor seed isolated from mouse model tauopathy, progressive supranuclear palsy postmortem samples. show BSN...
Pathological aggregation of tau and neuroinflammatory changes mark the clinical course Alzheimer's disease related tauopathies. To understand correlation between these pathological hallmarks functional deficits, we assessed behavioral physiological deficits in PS19 mouse model, a broadly utilized model tauopathy. At 9 months, mice have characteristic hyperactive behavior, decline motor strength, deterioration conditions marked by lower body temperature, reduced weight, an increase measures...
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder underlying dementia in geriatric population. AD manifests by two pathological hallmarks: extracellular amyloid-β (Aβ) peptide-containing senile plaques and intraneuronal neurofibrillary tangles comprised of aggregated hyperphosphorylated tau protein (p-tau). However, more than half cases also display presence α-synuclein (α-syn)-containing Lewy bodies. Conversely, bodies disorders have been reported to concomitant Aβ...
Pathological aggregation and propagation of hyperphosphorylated aberrant forms tau are critical features the clinical progression Alzheimer's disease other tauopathies. To better understand correlation between these pathological species progression, we profiled temporal seeding activity levels various phospho- conformational in brains two mouse models human Our findings indicate that is an early event occurs well before appearance AT8-positive NFT. Specifically, observed phosphorylation...
The aggregation and spreading of "tau-seeds" are key for the development progression tauopathies, including Alzheimer's disease. Here we describe steps to isolate analyze biochemically active tau-seeds from human, mouse, cell origin. We detail procedure soluble by size exclusion chromatography seeding assay. isolated tau-seed can be further analyzed determine interactome mass spectrometry. This workflow identifies protein-protein interactors tau-seeds, providing a useful tool finding new...
Alzheimer's disease (AD) and Parkinson's (PD) are multifactorial, chronic diseases involving neurodegeneration. According to recent studies, it is hypothesized that the intraneuronal postsynaptic accumulation of misfolded proteins such as α-synuclein (α-syn) tau, responsible for Lewy bodies (LB) tangles, respectively, disrupts neuron functions. Considering co-occurrence α-syn tau inclusions in brains patients afflicted with subtypes dementia LB disorders, discovery development small...
Abstract Background Tau aggregates, a hallmark of Alzheimer’s disease (AD) and other tauopathies, spread throughout the brain, contributing to neurodegeneration. How this propagation occurs remains elusive. Previous research suggests that tau‐seed interactors play crucial role. Based on this, study aimed identify novel in AD brains validate their impact vivo. Method control brain extracts were separated fractions by Size Exclusion Chromatography. Fractions with highest tau seeding activity,...
Abstract Background Close to 80 90% of subjects with AD also present cerebral amyloid angiopathy (CAA) a disease in which accumulation damages the vasculature an impairs blood flow. Since current therapies are targeting focusing on amyloid, we interested determine how decrease observed CAA and our aim is impact tau reduction pathogenesis. Method We crossed Tg‐FDD mice model Mapt ‐/‐ levels analyzed pathogenesis different genotypes though behavioral tests, histological morphometric assays...
Abstract Background Tau aggregation is the major cause of several neurodegenerative tauopathies. interaction with other proteins affects formation tau aggregates seeding activity but less known about its effects on tau‐seed properties. Our previous study revealed that Bassoon (BSN), a presynaptic protein, interacts tau‐seed, exacerbating toxicity in vivo. Bsn downregulation reduced spreading and overall pathology. Intriguingly, parallel associated missense mutations BSN patients, prompting...
Abstract Background Pathological tau aggregation is a defining histopathological feature of Alzheimer’s disease (AD) and other neurodegenerative diseases collectively known as tauopathies. The propagation pathological forms in AD patient brains has been shown to follow neuronal networks. However, the cellular mechanisms involved nature species spreading remain unclear. Method We performed an unbiased quantitative mass spectrometry‐based study identify proteins that specifically interact with...
Abstract Background Pathological tau aggregates are key features of Alzheimer’s disease and other tauopathies. The current research aims to understand how spread in AD patient brains, but the mechanisms remain unclear. Our recent‐published study found that protein Bassoon plays a role spreading pathology mouse model for tauopathy using mass spectrometry identify proteins interacting with seeds. Considering our finding enhancing relevance tau‐seed interactor on pathology, we aim characterize...
Abstract Background Tau aggregation is the underlying cause of several neurodegenerative tauopathies. Formation tau aggregates with seeding activity involves interactions other proteins, but unknown effects on tau‐seed properties. Our previous study found that Bassoon (BSN), a presynaptic protein, interacts tau‐seed, exacerbating its toxicity in vivo. Bsn downregulation reduced spreading and overall pathology. A also linked missense mutations BSN to 3‐ 4‐repeat patients. However, it how...
Abstract Background Tau aggregates are critical pathological features of Alzheimer’s disease (AD) and other tauopathies. An important focus research has been to understand the tau propagation in AD patient brains that follow neuronal networks. Despite knowledge acquired, cellular mechanism involved seeding still unclear. Unfortunately, nature species spreading precise seeding/template remains unknown. this uncertainty, some studies suggest a high molecular weight (HMW‐tau) is form...