Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SORLA upregulation suppresses global pathological effects in aged tauopathy mouse brain

ABSTRACT: A role for the type I transmembrane trafficking receptor SORLA in reducing Aβ levels has been well-established, however, virtually nothing is known with respect to whether and how SORLA can potentially affect tau pathology. Here, we show that transgenic SORLA upregulation (SORLA TG) can reverse pathological effects in aged PS19 (P301S tau) mouse brain, including tau phosphorylation, ventricle dilation, synapse loss, LTP impairment and glial hyperactivation. Proteomic analysis indicates reversion of PS19 profiles in PS19/SORLA TG hippocampus, including pathological changes in synapse-related proteins as well as key drivers of synaptic dysfunction such as Apoe and C1q. snRNAseq analysis reveals suppression of PS19-dependent signatures with SORLA upregulation, including proinflammatory induction of Plxnb1/Plxnb2 in glial cell types. PlxnB1/B2 expression as well as other neuroinflammatory features are exacerbated in PS19 hippocampus with SORLA deletion. Together, these results implicate a global role for SORLA in neuroprotection from tau toxicity in PS19 mouse brain.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Timothy Huang

LAB HEAD: Timothy Y. Huang

PROVIDER: PXD056276 | Pride | 2026-05-24

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	P001627_Tau_132.raw	Raw
	P001627_Tau_133.raw	Raw
	P001627_Tau_134.raw	Raw
	P001627_Tau_136.raw	Raw
	P001627_Tau_137.raw	Raw

Items per page:

1 - 5 of 31

Similar Datasets

SORLA upregulation suppresses global pathological effects in aged tauopathy mouse brain [snRNA-seq]

Project description:A role for the type I transmembrane trafficking receptor SORLA in reducing Aβ levels has been well-established, however, virtually nothing is known with respect to whether and how SORLA can potentially affect tau pathology. Here, we show that transgenic SORLA upregulation (SORLA TG) can reverse pathological effects in aged PS19 (P301S tau) mouse brain, including tau phosphorylation, ventricle dilation, synapse loss, LTP impairment and glial hyperactivation. Proteomic analysis indicates reversion of PS19 profiles in PS19/SORLA TG hippocampus, including pathological changes in synapse-related proteins as well as key drivers of synaptic dysfunction such as Apoe and C1q. snRNAseq analysis reveals suppression of PS19-dependent signatures with SORLA upregulation, including proinflammatory induction of Plxnb1/Plxnb2 in glial cell types. PlxnB1/B2 expression as well as other neuroinflammatory features are exacerbated in PS19 hippocampus with SORLA deletion. Together, these results implicate a global role for SORLA in neuroprotection from tau toxicity in PS19 mouse brain.

2026-05-24 | GSE278215 | GEO

SORLA upregulation suppresses global pathological effects in aged tauopathy mouse brain [GeoMX]

2026-05-24 | GSE278067 | GEO

Gene Expression of PS19 Tau transgenic mice

Project description:Expression of PS19 Tau Transgenic mice from hippocampus at different ages 3, 6, 9, and 12 months We used Affy arrays to understand the global expression profile of PS19 Tau transgenic mice

2018-08-28 | GSE89979 | GEO

Abundance of tRNA fragments in Tau-RNA complexes from Tau-mutant PS19 (human P301S Tau transgenic) mice hippocampus

Project description:We report the binding between tRNA fragments and Phosphorylated Tau pS396 from the hippocampus of WT controls and Tau-mutant PS19 (human P301S Tau transgenic) mice. We show tRNA fragments abundance in Tau-RNA complexes changes between the two groups. Specific tRNA fragment in the results of Real Time-qPCR were consistent with the small RNA microarray:5'tRF_GluCTC

2025-05-14 | GSE297027 | GEO

Complement C1q-dependent synapse elimination by astrocytes in a mouse model of Alzheimer's disease

Project description:Synapse loss and glial activation are hallmarks of Alzheimer's disease (AD). In Tau P301S transgenic mice, the complement pathway contributes to neuronal damage through microglial elimination of synapses. Here, we used unbiased proteomic profiling of postsynaptic density (PSD) fractions from Tau P301S mice in C1q-WT versus C1q knockout backgrounds to identify C1q-dependent changes at synapses. Integrative multi-omics analysis revealed that astrocyte- and microglia- specific proteins are increased in Tau P301S synapse fractions with age and in a C1q-dependent manner. The same set of glial proteins (including C1q, C4, Gpnmb, and S100a4) is elevated in human AD synaptic fractions, and C4 levels are raised in cerebrospinal fluid (CSF) from AD patients. Besides microglia, we show that astrocytes contribute substantially to excitatory and inhibitory synapse engulfment in Tau P301S hippocampus. Based on staining of synapse markers within lysosomes, astrocytes showed preference for excitatory synapses whereas microglia preferred to engulf inhibitory synapse markers. Genetic deletion of C1q reduced astrocytic eating of excitatory and inhibitory synapses in Tau P301S mice, and rescued synapse density. Together, our data indicate that astrocytes contact and phagocytose synapses in a C1q- dependent manner and thereby contribute to synapse loss and neurodegeneration in AD.

2021-11-03 | MSV000088313 | MassIVE

Mouse female hippocampus proteomics of Alzheimer Tg-SwDI Model

Project description:Cerebral Amyloid Angiopathy (CAA) is a significant comorbidity in almost all cases of Alzheimer’s disease (AD) and is unaddressed by current treatment regimens. We explored the Tg-SwDI mouse model which expresses human Amyloid Precursor Protein with the familial Swedish AD mutation as well as the vasculotropic Dutch and Iowa mutations leading to a phenotype of cognitive deficits with severe CAA. This is the first mapping of cerebral parenchymal proteomes of this model. In a cohort of presymptomatic mice both the cortex and hippocampus proteomes were mapped in male as well as female mice. In the four proteomes profound adaptations were identified, and previous findings of an early and severe pathology in Tg-SwDI female mice are reaffirmed on the molecular level. In addition, the effectiveness of two Carbonic Anhydrase Inhibitors (CAIs), Acetazolamide and Methazolamide, in preventing the observed molecular adaptations was evaluated. These repurposed drugs broadly prevented the proteome adaptations in the Tg-SwDI mice.

2025-05-07 | PXD055083 | Pride

The inhibition of LSD1 via sequestration contributes to tau-mediated neurodegeneration

Project description:In this dataset, we evalute the effect of modulating the levels of LSD1 in the PS19 tauopathy mouse (mouse that expresses the P301S mutated form of the human tau transgene). First we reduced the levels of LSD1 by crossing PS19 Tau mice with mice heterozygous for Lsd1. This results in an exacerbation of the neurodegenerative phenotype as well as an increase in the transcripational changes observed in taupoathy mice. Secondy, we overexprssed LSD1 in neurons of the adult tauopathy mouse through viral injection direclty into the hippocampus. This resulted in a reduce of neuronal cell death as well as the associated transcriptional changes.

2020-10-27 | GSE160151 | GEO

Hippocampal proteomic alteration in triple transgenic mouse model of Alzheimer’s disease: insights into the role of PINK 1 proteins in donepezil treatment Hippocampal proteomic alteration in triple transgenic mouse model of Alzheimer’s disease: insights into the role of PINK 1 proteins in donepezil treatment

Project description:Donepezil, an acetylcholinesterase (AChE) inhibitor, was approved by FDA for the symptomatic therapies of patients with Alzheimer’s disease (AD) in 1996. Although donepezil have been regarded as the standard and first-line treatment for AD, the capacity of such drugs to alter the underlying disease process is still unclear. In this study, we sought to explore the possible protective mechanism of donepezil in triple-transgenic Alzheimer’s disease (3×Tg-AD) mice model. 3×Tg-AD mice were treated for 4 months with donepezil (1.3 mg /kg) and its effects were evaluated by behavioral tests and molecular analysis. The cognition of donepezil-treated mice was restored significantly. Reduced levels of soluble and insoluble amyloid beta 1-40 (Aβ 1-40) and amyloid beta 1-42 (Aβ 1-42) as well as senile plaques were observed. Moreover, donepezil treatment prevented the dendritic spine loss in hippocampus neurons. We further investigated the effects of donepezil on the hippocampal protein of 3×Tg-AD mice by quantitative proteomics technology. Proteomic results indicated that donepezil significantly elevated the levels of PINK1, NFASC, MYLK2, and RASN in the hippocampus, and modulated axon guidance, mitophagy, mTOR signaling, and MAPK pathway. The results suggested that donepezil induced neuroprotective effects through multiple mechanisms.

2018-12-03 | PXD010604 | Pride

Protein kinase CK2α’ as a Dual Modulator of Immune Signaling and Synaptic Dysfunction in Tauopathy

Project description:Protein kinase CK2α’ is upregulated in patients with tau-associated dementias and in the PS19 mouse model of tauopathy. CK2α’ haploinsufficiency in the PS19 mouse model improved tau pathology, synaptic density, synaptic function, cognitive behavior and disease-associated microglia phenotypes. We hypothesized CK2α’ haploinsufficiency would impact dysregulated gene expression in the PS19 model. We found that CK2α’ haploinsufficiency led to enhanced synaptic gene network expression and enhance immune gene network expression.

2026-02-06 | GSE298505 | GEO

TFEB-vacuolar ATPase signaling regulates lysosomal activity and immune response in tauopathy

Project description:Transcription factor EB (TFEB) mediates gene expression through binding to the Coordinated Lysosome Expression And Regulation (CLEAR) sequence. We created a knock-in mouse line in which the CLEAR sequence of ATP6V1H was mutated. Crossing the CLEAR mutant with PS19 mice led to higher tau pathology but dampened glial cell activation. snRNA-seq revealed that the CLEAR mutant failed to be activated in tauopathy conditions.

2023-06-02 | GSE218728 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data