Proteomics

Dataset Information

6

Alzheimer Disease (AD) and AD model detergent insoluble proteomes


ABSTRACT: Characterizing the detergent insoluble brain proteome of sporadic late-onset Alzheimer’s disease (LOAD) has identified proteins and pathways associated with disease pathogenesis. Similar studies in early onset Alzheimer’s disease cases due to presenilin-1 mutations (PS1-EOAD), along with more detailed correlations with insoluble proteomes from LOAD and AD transgenic rodents, are limited. We therefore utilized quantitative proteomics to identify proteins that were significantly changing in the PS1-EOAD insoluble proteome versus controls. Comparison with the LOAD insoluble proteome identified common pathologic AD markers in addition to unique PS1-EOAD insoluble proteins. Similarly, weighted correlation network analysis (WGCNA) identified PS1-EOAD and LOAD co-expression modules with both like and disparate expression levels. Finally, we compared the human PS1-EOAD insoluble proteome to transgenic AD mouse and rat insoluble proteomes to understand how well these models mimic the human disease. Although many common AD pathologic findings were found in the rodents, there were multiple PS1-EOAD proteome changes not well recapitulated in the animal models. These proteomic studies highlight unique PS1-EOAD proteome changes as compared to LOAD and identify limitations to using AD transgenic rodents to study some aspects of AD.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo sapiens  

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Eric Dammer  

LAB HEAD: Nicholas T. Seyfried

PROVIDER: PXD005321 | Pride | 2019-06-25

REPOSITORIES: pride

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Publications

Changes in the detergent-insoluble brain proteome linked to amyloid and tau in Alzheimer's Disease progression.

Hales Chadwick M CM   Dammer Eric B EB   Deng Qiudong Q   Duong Duc M DM   Gearing Marla M   Troncoso Juan C JC   Thambisetty Madhav M   Lah James J JJ   Shulman Joshua M JM   Levey Allan I AI   Seyfried Nicholas T NT  

Proteomics 20161201 23


Despite a key role of amyloid-beta (Aβ) in Alzheimer's disease (AD), mechanisms that link Aβ plaques to tau neurofibrillary tangles and cognitive decline still remain poorly understood. The purpose of this study was to quantify proteins in the sarkosyl-insoluble brain proteome correlated with Aβ and tau insolubility in the asymptomatic phase of AD (AsymAD) and through mild cognitive impairment (MCI) and symptomatic AD. Employing label-free mass spectrometry-based proteomics, we quantified 2711 s  ...[more]

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