Olfactory bulb proteome dynamics during the progression of sporadic Alzheimer's disease: identification of common and distinct olfactory targets across Alzheimer-related co-pathologies
| Autor: | Teresa Tuñon, Isidro Ferrer, Maria-Rosario Luquin, Enrique Santamaría, Estela Perez-Valderrama, Xabier Martínez de Morentin, Joaquín Fernández-Irigoyen, María Victoria Zelaya |
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| Přispěvatelé: | Universitat de Barcelona |
| Rok vydání: | 2015 |
| Předmět: |
Male
Proteomics Pathology medicine.medical_specialty Proteome Blotting Western Proteòmica Biology Mass Spectrometry Progressive supranuclear palsy Research Paper: Gerotarget (Focus on Aging) Alzheimer Disease medicine Humans Dementia Protein Interaction Maps Aged Aged 80 and over Gerotarget Neurodegeneration neurodegeneration Brain Neurodegenerative Diseases Frontotemporal lobar degeneration Middle Aged Alzheimer's disease medicine.disease Immunohistochemistry Olfactory Bulb Metabolisme Olfactory bulb Malaltia d'Alzheimer Metabolism Oncology Alzheimer Disease Progression Female Autopsy Supranuclear Palsy Progressive |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname Oncotarget Dipòsit Digital de la UB Universidad de Barcelona ResearcherID |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.6254 |
| Popis: | Olfactory dysfunction is present in up to 90% of Alzheimer's disease (AD) patients. Although deposition of hyperphosphorylated tau and β-amyloid substrates are present in olfactory areas, the molecular mechanisms associated with decreased smell function are not completely understood. We have applied mass spectrometry-based quantitative proteomics to probe additional molecular disturbances in postmortem olfactory bulbs (OB) dissected from AD cases respect to neurologically intact controls (n=20, mean age 82.1 years). Relative proteome abundance measurements have revealed protein interaction networks progressively disturbed across AD stages suggesting an early imbalance in splicing factors, subsequent interrupted cycling of neurotransmitters, alteration in toxic and protective mechanisms of β-amyloid, and finally, a mitochondrial dysfunction together with disturbance in neuron-neuron adhesion. We also present novel molecular findings in the OB in an autopsy cohort composed by Lewy body disease (LBD), frontotemporal lobar degeneration (FTLD), mixed dementia, and progressive supranuclear palsy (PSP) cases (n = 41, mean age 79.7 years). Olfactory mediators deregulated during the progression of AD such as Visinin-like protein 1, RUFY3 protein, and Copine 6 were also differentially modulated in the OB in LBD, FTLD, and mixed dementia. Only Dipeptidyl aminopeptidase-like protein 6 showed a specific down-regulation in AD. However, no differences were observed in the olfactory expression of this protein panel in PSP subjects. This study demonstrates an olfactory progressive proteome modulation in AD, unveiling cross-disease similarities and differences especially for specific proteins involved in dendritic and axonic distributions that occur in the OB during the neurodegenerative process. |
| Databáze: | OpenAIRE |
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