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Human PSP synaptoneurosome proteomics

ABSTRACT: Investigation into PSP using proteomic techniques. Through the use of different human brain preps, the differences between those with Progressive supranuclear palsy and those without will be compared

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Bethany Geary

LAB HEAD: Robert McGeachan

PROVIDER: PXD048456 | Pride | 2025-08-25

REPOSITORIES: Pride

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			Action	DRS
	20231005_DRIX055_1.raw	Raw
	20231005_DRIX055_10.raw	Raw
	20231005_DRIX055_11.raw	Raw
	20231005_DRIX055_12.raw	Raw
	20231005_DRIX055_13.raw	Raw

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Publications

Evidence for trans-synaptic propagation of oligomeric tau in human progressive supranuclear palsy.

McGeachan Robert I RI Keavey Lois L Simzer Elizabeth M EM Chang Ya Yin YY Rose Jamie L JL Spires-Jones Maxwell P MP Gilmore Mollie M Holt Kristjan K Meftah Soraya S Ravingerova Natalia N Scutariu Cristina C Taylor Lewis W LW King Declan D Tzioras Makis M Tulloch Jane J Booker Sam A SA Liaquat Imran I Hindley-Pollock Nicole N Geary Bethany B Smith Colin C Brennan Paul M PM Durrant Claire S CS Spires-Jones Tara L TL

Nature neuroscience 20250716 8

In the neurodegenerative disease progressive supranuclear palsy (PSP), tau pathology progresses through the brain in a stereotypical spatiotemporal pattern, and where tau pathology appears, synapses are lost. We tested the hypothesis that pathological tau contributes to synapse loss and may spread through the brain by moving from presynapses to postsynapses. Using postmortem PSP brain samples and a living human brain slice culture model, we observe pathological tau in synaptic pairs and evidence ...[more]

PMID: 40670683

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Human brain homogenate and synaptoneurosome proteomics

Project description:Investigation into PSP using proteomic techniques. Through the use of different human brain preps, the differences between those with Progressive supranuclear palsy and those without will be compared

2025-08-25 | PXD047282 | Pride

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Project description:Genome-wide DNA methylation profiling in progressive supranuclear palsy (PSP)

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CROPSeq of Putative AD- and PSP-associated cis-Regulatory Regions in iPSC-derived Neurons and Microglia

Project description:We performed a pooled CRISPRi screen (CROP-seq) and genome editing to validate 19 genetic variants prioritized from massively parallel reporter assays to screen 5,706 polymorphisms from genome-wide association studies for both Alzheimer’s disease (AD) and Progressive Supranuclear Palsy (PSP) across 11 distinct loci. This allowed us to pinpoint regulatory targets in a cell-type specific manner.

2022-07-05 | GSE207099 | GEO

A splice isoform signature of ParkinsonM-bM-^@M-^Ys disease in peripheral blood

Project description:In these studies, we used splice variant-specific microarrays manufactured by the ExonHit company ( www.exonhit.com) on the Affymetrix platform. The goal was to identify splice isoforms whose expression is altered in whole blood of early-stage ParkinsonM-bM-^@M-^Ys disease patients compared to healthy and neurodegenerative disease controls. The study included 19 cases of ParkinsonM-bM-^@M-^Ys disease (PD) samples, 4 of multiple system atrophy (MSA), 4 progressive supranuclear palsy (PSP) and 10 healthy controls. Thirteen splice variants were confirmed in quantitative polymerase chain reactions and used to classify blinded samples from ParkinsonM-bM-^@M-^Ys disease patients and controls with 90% accuracy and 94% sensitivity. In these studies, we used splice variant-specific microarrays manufactured by the ExonHit company ( www.exonhit.com) on the Affymetrix platform. The study included 19 cases of ParkinsonM-bM-^@M-^Ys disease (PD) samples and 20 control samples including 4 cases of multiple system atrophy (MSA), 4 progressive supranuclear palsy (PSP) and 12 healthy controls. Splice isoforms differentially expressed in PD vs any other control group were identified and validated using real-time quantitative PCR on two independent sets of 33 coded and 53 blinded samples.

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An Epigenetic Signature in Peripheral Blood Associated with Neurodegenerative Tauopathy and the Risk-Associated Haplotype on 17q21.31

Project description:Progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD) are two neurodegenerative diseases linked, at the pathologic and genetic level, to the macrutubule associated protein tau. We identified and replicated a dose-dependent effect of the risk-associated H1 haplotype on methylation levels within the region in independent datasets in blood and brain. These data reveal that the H1 haplotype increases risk for tauopathy via differential methylation, indicating a mediating role for methylation in dementia pathophysiology. We studied epigenetic changes (DNA methylation levels) in peripheral blood from patients with PSP, FTD, and unaffected controls. Analysis of genome-wide methylation patterns revealed significant differentially methylated probes in patients versus unaffected controls.

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Identification of potential biomarkers for patients with neurodegenerative parkinsonian syndromes using serum cytokine microarray analysis; series 6

Project description:Background: Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum cytokine-array to screen for potential molecular biomarkers for Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Methodology/Principal Findings: Serum samples were obtained from patients with clinical diagnoses of PD (n=117), MSA (n=31) and PSP/CBS (n=38) and 99 controls. Cytokine profiles of sera of patients and controls were analyzed with a semiquantitative human cytokine antibody array. In a next step, significantly altered cytokines were individually validated by immunoassays. The cytokine array revealed a significantly altered expression of 12 cytokines. Immunoassay validation confirmed a significant increase of PDGF-BB in PSP/CBS, MSA and PD and a decrease of Prolactin in PD (Kruskal-Wallis p<0.05). A multivariate analysis taking into account diagnoses anti-Parkinsonian treatment, sex and age revealed that PDGF-BB levels were influenced only by the diagnoses (p<0.001), whereas Prolactin levels were influenced only by anti-Parkinsonian treatment (p<0.001). These findings could be corroborated by a subgroup analysis in untreated patients. Conclusions/Significance: In our unbiased cytokine array screening approach we found PDGF-BB to be elevated in PSP/CBS, MSA and PD. Increased PDGF-BB levels might be of relevance in a model of molecular biomarkers for Parkinsonian syndromes. Screen serum samples from patients with Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome, multisystem atrophy and controls for deregulation of serum proteins using a cytokine-array detecting 174 secreted signaling proteins.

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Project description:A mild olfactory dysfunction has been observed in frontotemporal dementias (FTD). However, the underlying molecular mechanisms associated to this deficit are poorly understood. Here, we applied mass spectrometry-based quantitative proteomics to analyse pathological effects on the olfactory bulb (OB) from progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration TDP43 proteinopathy (FTLD-TDP) subjects

2022-02-15 | PXD011446 | Pride