Dataset Information

Time-course global proteome analyses in the APPNL-F mouse model of Alzheimer disease

ABSTRACT: A hallmark of Alzheimer Disease is the accumulation of aggregation-prone amyloid beta peptides, which can assemble into smaller aggregates and deposit in the form of amyloid plaques. Here we used the recently introduced APPNL-F mouse model of Alzheimer Disease, which faithfully recapitulates the amyloid beta pathology of the disease, to identify early changes to the global proteome. Using a workflow that interrogated the brain proteome of these mice by quantitative mass spectrometry at five, ten and fifteen months of age.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Alzheimer's Disease

SUBMITTER: Declan Williams

LAB HEAD: Gerold Schmitt-Ulms

PROVIDER: PXD004439 | Pride | 2017-08-02

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	Mouse_brain_10months_APP-NL-F-NL-F_versus_APP-wt-NL-F_global_TMT_6_7_8_9_0_1_C18_1-3_SCX_1-3.msf	Msf
	Mouse_brain_10months_APP-NL-F-NL-F_versus_APP-wt-NL-F_global_TMT_6_7_8_9_0_1_C18_1.raw	Raw
	Mouse_brain_10months_APP-NL-F-NL-F_versus_APP-wt-NL-F_global_TMT_6_7_8_9_0_1_C18_2.raw	Raw
	Mouse_brain_10months_APP-NL-F-NL-F_versus_APP-wt-NL-F_global_TMT_6_7_8_9_0_1_C18_3.raw	Raw
	Mouse_brain_10months_APP-NL-F-NL-F_versus_APP-wt-NL-F_global_TMT_6_7_8_9_0_1_SCX_1.raw	Raw

Items per page:

1 - 5 of 19

Publications

Time-course global proteome analyses reveal an inverse correlation between Aβ burden and immunoglobulin M levels in the APPNL-F mouse model of Alzheimer disease.

Wang Hansen H Williams Declan D Griffin Jennifer J Saito Takashi T Saido Takaomi C TC Fraser Paul E PE Rogaeva Ekaterina E Schmitt-Ulms Gerold G

PloS one 20170823 8

Alzheimer disease (AD) stands out amongst highly prevalent diseases because there is no effective treatment nor can the disease be reliably diagnosed at an early stage. A hallmark of AD is the accumulation of aggregation-prone amyloid β peptides (Aβ), the main constituent of amyloid plaques. To identify Aβ-dependent changes to the global proteome we used the recently introduced APPNL-F mouse model of AD, which faithfully recapitulates the Aβ pathology of the disease, and a workflow that interrog ...[more]

PMID: 28832675

Similar Datasets

Project description:Extracellular senile plaques of amyloid beta (Abeta) are a pathological hallmark in brain of patients with Alzheimer`s Disease (AD). Abeta is generated by the amyloidogenic processing of the amyloid precursor protein (APP). Concomitant to Abeta load, AD brain is characterized by an increase in protein level and activity of the angiotensin-converting enzyme (ACE). ACE inhibitors are a widely used class of drugs with established benefits for patients with cardiovascular disease. However, the role of ACE and ACE inhibition in the development of Abeta plaques and the process of AD-related neurodegeneration is not clear since ACE was reported to degrade Abeta. To investigate the effect of ACE inhibition on AD-related pathomechanisms, we used Tg2576 mice with neuron-specific expression of APPSwe as AD model. From 12 months of age, substantial Abeta plaque load accumulates in the hippocampus of Tg2576 mice as a brain region, which is highly vulnerable to AD-related neurodegeneration. The effect of central ACE inhibition was studied by treatment of 12 month-old Tg2576 mice for six months with the brain penetrating ACE inhibitor captopril. At an age of 18 months, hippocampal gene expression profiling was performed of captopril-treated Tg2576 mice relative to untreated 18 month-old Tg2576 controls with high Abeta plaque load. As an additional control, we used 12 month-old Tg2576 mice with low Abeta plaque load. Whole genome microarray gene expression profiling revealed gene expression changes induced by the brain-penetrating ACE inhibitor captopril, which could reflect the neuro-regenerative potential of central ACE inhibition. Microarray gene expression profiling was performed of hippocampi isolated from aged, 18 month-old Tg2576 (APPSwe-transgenic) AD mice with high Abeta plaque load relative to age-matched Tg2576 mice, which were treated for 6 months with the centrally active ACE inhibitor captopril. Another study group consisted of 12 month-old Tg2576 mice with low Abeta plaque load. In total, three study groups were analyzed, i.e. (i) 18 month-old untreated Tg2576 mice with high Abeta plaque load, (ii) age-matched Tg2576 mice treated for 6 months with the brain-penetrating ACE inhibitor captopril (20 mg/kg body weight/day in drinking water), and (iii) untreated 12 month-old Tg2576 mice with low Abeta plaque load reflecting the time point when captopril treatment was initiated. Two biological replicates were made of each group, and total hippocampal RNA of four mice was pooled for one gene chip.