Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deep Multilayer Tissue Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression, human data

ABSTRACT: The molecular networks underlying Alzheimer’s disease (AD) are not well-defined. We present temporal profiling of >14,000 proteins and >34,000 phosphosites at the asymptomatic and symptomatic stages of AD, deep proteomics analysis of transgenic mouse models.

INSTRUMENT(S): LTQ Orbitrap Elite, Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Junmin Peng

PROVIDER: MSV000096123 | MassIVE | Thu Oct 17 20:52:00 BST 2024

SECONDARY ACCESSION(S): PXD007985

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Publications

Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.

Bai Bing B Wang Xusheng X Li Yuxin Y Chen Ping-Chung PC Yu Kaiwen K Dey Kaushik Kumar KK Yarbro Jay M JM Han Xian X Lutz Brianna M BM Rao Shuquan S Jiao Yun Y Sifford Jeffrey M JM Han Jonghee J Wang Minghui M Tan Haiyan H Shaw Timothy I TI Cho Ji-Hoon JH Zhou Suiping S Wang Hong H Niu Mingming M Mancieri Ariana A Messler Kaitlynn A KA Sun Xiaojun X Wu Zhiping Z Pagala Vishwajeeth V High Anthony A AA Bi Wenjian W Zhang Hui H Chi Hongbo H Haroutunian Vahram V Zhang Bin B Beach Thomas G TG Yu Gang G Peng Junmin J

Neuron 20200108 6

Alzheimer's disease (AD) displays a long asymptomatic stage before dementia. We characterize AD stage-associated molecular networks by profiling 14,513 proteins and 34,173 phosphosites in the human brain with mass spectrometry, highlighting 173 protein changes in 17 pathways. The altered proteins are validated in two independent cohorts, showing partial RNA dependency. Comparisons of brain tissue and cerebrospinal fluid proteomes reveal biomarker candidates. Combining with 5xFAD mouse analysis, ...[more]

PMID: 31926610

Similar Datasets

Deep Multilayer Tissue Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression

Project description:The molecular networks underlying Alzheimer’s disease (AD) are not well-defined. We present temporal profiling of >14,000 proteins and >34,000 phosphosites at the asymptomatic and symptomatic stages of AD, deep proteomics analysis of transgenic mouse models.

2019-11-11 | PXD007974 | Pride

Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression

2020-04-16 | PXD018590 | Pride

Deep Multilayer Tissue Proteomics Identifies Molecular Networks in Alzheimer’s Disease Progression, human data

2019-11-11 | PXD007985 | Pride

Global quantitative analysis of the human brain proteome and phosphoproteome in Alzheimer’s diseaseGlobal quantitative analysis of the human brain proteome and phosphoproteome in Alzheimer’s disease

Project description:Alzheimer’s disease (AD) is characterized by an early, asymptomatic phase (AsymAD) in which individuals exhibit amyloid-beta (Aβ) plaque accumulation in the absence of clinically detectable cognitive decline. Here we report an unbiased multiplex quantitative proteomic and phosphoproteomic analysis using tandem mass tag (TMT) isobaric labeling of human post-mortem cortex (n=27) across pathology-free controls, AsymAD and symptomatic AD individuals. With off-line high-pH fractionation and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) on an Orbitrap Lumos mass spectrometer, we identified 11,378 protein groups across three TMT 11-plex batches. Immobilized metal affinity chromatography (IMAC) was used to enrich for phosphopeptides from the same TMT-labeled cases and 51,736 phosphopeptides were identified. Of these, 48,992 were quantified by TMT reporter ions representing 33,652 unique phosphosites. Two reference standards in each TMT 11-plex were included to assess intra- and inter-batch variance at the protein and peptide level. This comprehensive human brain proteome and phosphoproteome dataset will serve as a valuable resource for the identification of biochemical, cellular and signaling pathways altered during AD progression.

2020-09-16 | PXD020296 | Pride

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

Co-expression network analysis of frontal cortex during the progression of Alzheimer’s disease

Project description:Using WGCNA and enrichment analyses to identify pathway level differences between individuals with no cognitive impairment, mild cognitive impairment, and Alzheimer’s disease. Frozen frontal cortex (BA10) tissue from NCI, MCI, and mild/moderate AD cases (n = 12/group) representing both genders was acquired postmortem from participants in the Rush Religious Orders Study, a longitudinal clinical pathologic study of aging and AD in elderly Catholic clergy

2021-10-15 | GSE185909 | GEO

Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer’s disease

Project description:Astrocytes are crucial to brain homeostasis, yet their changes along the spatiotemporal progression of Alzheimer’s disease (AD) neuropathology remain largely unexplored. Here, we performed single- nucleus RNA-sequencing of 628,943 astrocytes from five brain regions representing the stereotypical progression of AD pathology, across 32 donors spanning the entire normal aging-to-severe AD continuum. We discovered astrocyte gene expression trajectories that are differentially activated or suppressed at various regions and disease stages. We mapped out several unique astrocyte subclusters that exhibited varying responses to neuropathology across the AD-vulnerable neural network (spatial axis) or AD pathology stage (temporal axis). The proportion of homeostatic, intermediate, and reactive astrocytes changed solely along the spatial axis, whereas two other unique subclusters changed along the temporal axis. One of these, a trophic factor-rich subcluster, declined along pathology stage, whereas the other, defined by proteostasis and metabolic genes, increased in late-stage but unexpectedly returned to baseline levels in end-stage, suggesting exhaustion of response with chronic exposure to neuropathology. Our study underscores the complex and dynamic nature of astrocytic responses in AD and our findings are available at https://ad-progression-atlas.partners.org

2024-07-22 | GSE268599 | GEO

Quantitative phosphoproteomics uncovers dysregulated kinase networks in Alzheimer’s disease

Project description:Alzheimer’s disease (AD) is a form of dementia characterized by amyloid-β plaques and Tau neurofibrillary tangles that progressively disrupt neural circuits in the brain. Using mass spectrometry, we performed a combined analysis of the tyrosine, serine, and threonine phosphoproteome, and proteome of post-mortem brain tissue from AD patients and aged matched controls. We used a data-centric approach to identify co-correlated signaling networks associated with cellular and pathological changes. We identified two independent pathology clusters that were associated with Tau and oligodendrocyte pathologies. We observed phosphorylation sites on known Tau-kinases as well as other novel signaling factors that were associated with these clusters. Together, these results build a map of pathology-associated phosphorylation signaling activation events occurring in AD.

2021-05-25 | PXD020087 | Pride

Aging African Green Monkeys manifest transcriptional, pathological, and cognitive hallmarks of human Alzheimer’s disease

Project description:While many preclinical models of Alzheimer’s disease (AD) have been reported, none fully recapitulate the disease. In an effort to identify an appropriate preclinical disease model, we characterized age-related changes in two higher order species, the African Green Monkey (AGM) and the rhesus macaque. Gene expression profiles in the dorsolateral prefrontal cortex and the visual cortex showed age-related changes in AGMs that are strikingly reminiscent of AD, whereas aged rhesus were most similar to healthy elderly humans. Biochemically, age-related changes in AGM cerebrospinal fluid levels of tau, phospho-tau and amyloid beta were consistent with AD. Histologically, aged AGMs displayed pathological hallmarks of the disease, plaques, and two AGMs showed evidence of neurofibrillary tangle-like structures. We hypothesized and confirmed that AGMs have age-related cognitive deficits via a prefrontal cortex-dependent cognition test, and that symptomatic treatments which improve cognition in AD patients show efficacy in AGMs. These data suggest that the AGM could represent a novel and improved translational model to assist in the development of therapeutics for AD.

2018-02-01 | GSE108282 | GEO

Single-cell sequencing of cerebral organoids with familial Alzheimer’s disease (AD) mutation in PSEN1 and non-demented control

Project description:We set up a 3D model based on iPSCs derived from patients with familial forms of Alzheimer’s disease (AD) and healthy non-demented control. We created cerebral organoids (COs), verified their ability to mimic AD in vitro, and used it to explore early events and the progression of AD pathogenesis. Our data reveal that despite similar expression of cell-type-specific genes during CO maturation in vitro, AD-iPSCs derived COs show limited tissue patterning and altered cellular development. These findings complement unique single-cell sequencing data of AD-iPSCs derived COs confirming this observation and uncovering that a sub-set of neurons in AD-iPSCs likely differentiates prematurely while at the same time retaining the expression of progenitor marker PAX6.

2022-07-01 | E-MTAB-11438 | biostudies-arrayexpress

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