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

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Lingyan Ping ◽  
Sean R. Kundinger ◽  
Duc M. Duong ◽  
Luming Yin ◽  
Marla Gearing ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Immobilized Metal Affinity Chromatography ◽  
Tandem Mass ◽  
Metal Affinity ◽  
Tandem Mass Tag ◽  
Peptide Level ◽  
Brain Proteome ◽  
Asymptomatic Phase

Abstract 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.

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

2020 ◽  
Author(s):  
Lingyan Ping ◽  
Sean R. Kundinger ◽  
Duc M. Duong ◽  
Luming Yin ◽  
Marla Gearing ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Immobilized Metal Affinity Chromatography ◽  
Tandem Mass ◽  
Metal Affinity ◽  
Tandem Mass Tag ◽  
Peptide Level ◽  
Brain Proteome ◽  
Asymptomatic Phase

AbstractAlzheimer’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.

scholarly journals 27-Plex Tandem Mass Tag Mass Spectrometry for Profiling Brain Proteome in Alzheimer’s Disease

2020 ◽  
Vol 92 (10) ◽  
pp. 7162-7170 ◽  
Author(s):  
Zhen Wang ◽  
Kaiwen Yu ◽  
Haiyan Tan ◽  
Zhiping Wu ◽  
Ji-Hoon Cho ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tandem Mass ◽  
Tandem Mass Tag ◽  
Brain Proteome ◽  
Mass Tag

Phenylalanine Metabolism is Dysregulated in Human Hippocampus with Alzheimer’s Disease Related Pathological Changes

2021 ◽  
pp. 1-14
Author(s):  
Pan Liu ◽  
Qian Yang ◽  
Ning Yu ◽  
Yan Cao ◽  
Xue Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Pathological Examination ◽  
Pathological Changes ◽  
Targeted Metabolomics ◽  
Phenylpyruvic Acid ◽  
Postmortem Human Brain ◽  
Metabolic Dysregulation ◽  
Phenylalanine Metabolism

Background: Alzheimer’s disease (AD) is one of the most challenging diseases causing an increasing burden worldwide. Although the neuropathologic diagnosis of AD has been established for many years, the metabolic changes in neuropathologic diagnosed AD samples have not been fully investigated. Objective: To elucidate the potential metabolism dysregulation in the postmortem human brain samples assessed by AD related pathological examination. Methods: We performed untargeted and targeted metabolomics in 44 postmortem human brain tissues. The metabolic differences in the hippocampus between AD group and control (NC) group were compared. Results: The results show that a pervasive metabolic dysregulation including phenylalanine metabolism, valine, leucine, and isoleucine biosynthesis, biotin metabolism, and purine metabolism are associated with AD pathology. Targeted metabolomics reveal that phenylalanine, phenylpyruvic acid, and N-acetyl-L-phenylalanine are upregulated in AD samples. In addition, the enzyme IL-4I1 catalyzing transformation from phenylalanine to phenylpyruvic acid is also upregulated in AD samples. Conclusion: There is a pervasive metabolic dysregulation in hippocampus with AD-related pathological changes. Our study suggests that the dysregulation of phenylalanine metabolism in hippocampus may be an important pathogenesis for AD pathology formation.

P3-383: TNF expressing cells in the subependymal zone of the third ventricle of aged mouse and human brain with Alzheimer's disease pathology

2008 ◽  
Vol 4 ◽  
pp. T633-T634
Author(s):  
Ivica Granic ◽  
Csaba Nyakas ◽  
Gabor G. Kovacs ◽  
Paul G.M. Luiten ◽  
Ulrich L.M. Eisel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Third Ventricle ◽  
Aged Mouse ◽  
The Third ◽  
Subependymal Zone

scholarly journals Luminex-based quantification of Alzheimer’s disease neuropathologic change in formalin-fixed post-mortem human brain tissue

2018 ◽  
Vol 99 (7) ◽  
pp. 1056-1067
Author(s):  
C. Dirk Keene ◽  
Angela M. Wilson ◽  
Mitchell D. Kilgore ◽  
Lauren T. Bruner ◽  
Nadia O. Postupna ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Brain Tissue ◽  
Post Mortem ◽  
Human Brain Tissue ◽  
Formalin Fixed

scholarly journals Dimensional Changes in Lipid Rafts from Human Brain Cortex Associated to Development of Alzheimer’s Disease. Predictions from an Agent-Based Mathematical Model

2021 ◽  
Vol 22 (22) ◽  
pp. 12181
Author(s):  
Guido Santos ◽  
Mario Díaz
Keyword(s):  
Alzheimer’S Disease ◽  
Mathematical Model ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Lipid Rafts ◽  
Brain Cortex ◽  
Clinical Symptoms ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Human Brain Cortex

Alzheimer’s disease (AD) is a neurodegenerative disease caused by abnormal functioning of critical physiological processes in nerve cells and aberrant accumulation of protein aggregates in the brain. The initial cause remains elusive—the only unquestionable risk factor for the most frequent variant of the disease is age. Lipid rafts are microdomains present in nerve cell membranes and they are known to play a significant role in the generation of hallmark proteinopathies associated to AD, namely senile plaques, formed by aggregates of amyloid β peptides. Recent studies have demonstrated that human brain cortex lipid rafts are altered during early neuropathological phases of AD as defined by Braak and Braak staging. The lipid composition and physical properties of these domains appear altered even before clinical symptoms are detected. Here, we use a coarse grain molecular dynamics mathematical model to predict the dimensional evolution of these domains using the experimental data reported by our group in human frontal cortex. The model predicts significant size and frequency changes which are detectable at the earliest neuropathological stage (ADI/II) of Alzheimer’s disease. Simulations reveal a lower number and a larger size in lipid rafts from ADV/VI, the most advanced stage of AD. Paralleling these changes, the predictions also indicate that non-rafts domains undergo simultaneous alterations in membrane peroxidability, which support a link between oxidative stress and AD progression. These synergistic changes in lipid rafts dimensions and non-rafts peroxidability are likely to become part of a positive feedback loop linked to an irreversible amyloid burden and neuronal death during the evolution of AD neuropathology.

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