Dataset Information

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]

PMID: 26194619

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Project description:Krohn2011 - Cerebral amyloid-β proteostasis regulated by membrane transport protein ABCC1 This model is described in the article: Cerebral amyloid-β proteostasis is regulated by the membrane transport protein ABCC1 in mice. Krohn M, Lange C, Hofrichter J, Scheffler K, Stenzel J, Steffen J, Schumacher T, Brüning T, Plath AS, Alfen F, Schmidt A, Winter F, Rateitschak K, Wree A, Gsponer J, Walker LC, Pahnke J. J. Clin. Invest. 2011 Oct; 121(10): 3924-3931 Abstract: In Alzheimer disease (AD), the intracerebral accumulation of amyloid-β (Aβ) peptides is a critical yet poorly understood process. Aβ clearance via the blood-brain barrier is reduced by approximately 30% in AD patients, but the underlying mechanisms remain elusive. ABC transporters have been implicated in the regulation of Aβ levels in the brain. Using a mouse model of AD in which the animals were further genetically modified to lack specific ABC transporters, here we have shown that the transporter ABCC1 has an important role in cerebral Aβ clearance and accumulation. Deficiency of ABCC1 substantially increased cerebral Aβ levels without altering the expression of most enzymes that would favor the production of Aβ from the Aβ precursor protein. In contrast, activation of ABCC1 using thiethylperazine (a drug approved by the FDA to relieve nausea and vomiting) markedly reduced Aβ load in a mouse model of AD expressing ABCC1 but not in such mice lacking ABCC1. Thus, by altering the temporal aggregation profile of Aβ, pharmacological activation of ABC transporters could impede the neurodegenerative cascade that culminates in the dementia of AD. This model is hosted on BioModels Database and identified by: BIOMD0000000618. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Proteomics of Alzheimer's Disease mouse models - control dataset

Publications

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

Similar Datasets

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