Proteomics

Dataset Information

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Proteomics of Alzheimer's Disease mouse models - control dataset


ABSTRACT: Alzheimer’s disease (AD) is a neurodegenerative disease displaying plaques formed by the neurotoxic amyloid β-peptide (Aβ), and intracellular neurofibrillary tangles consisting of protein tau. However, how these pathologies relates to the massive neuronal death that occurs in AD brains remain elusive. Neprilysin is the major A degrading enzyme and a lack thereof increases A levels in the brain twofold. To identify altered protein expression levels induced by increased Aβ levels, we performed a proteomic analysis of the brain of the AD mouse model APPsw and compared it to that of APPsw mice lacking neprilysin. To this end we established an LC-MS/MS method to analyze brain homogenate, using an 18O-labeled internal standard to accurately quantify the protein levels. To distinguish between alterations in protein levels directly caused by increased A levels and those induced by neprilysin deficiency independently of A, the brain proteome of neprilysin deficient APPsw mice was compared to that of neprilysin deficient mice. By this approach we identified approximately 600 proteins and could quantify the levels of 300 of these. Pathway analysis showed that many of the proteins with altered expression were involved in neurological disorders, and that tau, presenilin and APP were key regulators in the identified networks. The data have been deposited to the ProteomeXchange Consortium with identifier PXD000968. Interestingly, the levels of several proteins, including some not previously reported to be associated with AD, were associated with increased A levels.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Per Nilsson  

LAB HEAD: Per Nilsson

PROVIDER: PXD001786 | Pride | 2015-07-29

REPOSITORIES: Pride

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Publications

Loss of neprilysin alters protein expression in the brain of Alzheimer's disease model mice.

Nilsson Per P   Loganathan Krishnapriya K   Sekiguchi Misaki M   Winblad Bengt B   Iwata Nobuhisa N   Saido Takaomi C TC   Tjernberg Lars O LO  

Proteomics 20150813 19


Alzheimer's disease (AD) is a neurodegenerative disease displaying extracellular plaques formed by the neurotoxic amyloid β-peptide (Aβ), and intracellular neurofibrillary tangles consisting of protein tau. However, how these pathologies relate to the massive neuronal death that occurs in AD brains remain elusive. Neprilysin is the major Aβ-degrading enzyme and a lack thereof increases Aβ levels in the brain twofold. To identify altered protein expression levels induced by increased Aβ levels, w  ...[more]

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