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http://hdl.handle.net/1942/28434
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DC Field | Value | Language |
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dc.contributor.author | Rosenberger, Andrea F.N. | - |
dc.contributor.author | Hilhorst, Riet | - |
dc.contributor.author | Coart, Elisabeth | - |
dc.contributor.author | GARCIA BARRADO, Leandro | - |
dc.contributor.author | Naji, Faris | - |
dc.contributor.author | Rozemuller, Annemieke J.M. | - |
dc.contributor.author | Van der Flier, Wiesje M. | - |
dc.contributor.author | Scheltens, Philip | - |
dc.contributor.author | Hoozemans, Jeroen J.M. | - |
dc.contributor.author | Van der Vies, Saskia M. | - |
dc.date.accessioned | 2019-06-18T08:10:28Z | - |
dc.date.available | 2019-06-18T08:10:28Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Journal of Alzheimer's disease, 49(4), p. 927-943 | - |
dc.identifier.issn | 1387-2877 | - |
dc.identifier.uri | http://hdl.handle.net/1942/28434 | - |
dc.description.abstract | Alzheimer’s disease (AD) is characterized by a long pre-clinical phase (20–30 years), during which significant brain pathology manifests itself. Disease mechanisms associated with pathological hallmarks remain elusive. Most processes associated with AD pathogenesis, such as inflammation, synaptic dysfunction, and hyper-phosphorylation of tau are dependent on protein kinase activity. The objective of this study was to determine the involvement of protein kinases in AD pathogenesis. Protein kinase activitywas determined in postmortem hippocampal brain tissue of 60 patients at various stages ofADand 40 nondemented controls (Braak stages 0-VI) using a peptide-based microarray platform. We observed an overall decrease of protein kinase activity that correlated with disease progression. The phosphorylation of 96.7% of the serine/threonine peptides and 37.5% of the tyrosine peptides on the microarray decreased significantly with increased Braak stage (p-value <0.01). Decreased activity was evident at pre-clinical stages of AD pathology (Braak I-II). Increased phosphorylation was not observed for any peptide. STRING analysis in combination with pathway analysis and identification of kinases responsible for peptide phosphorylation showed the interactions between well-known proteins in AD pathology, including the Ephrin-receptor A1 (EphA1), a risk gene for AD, and sarcoma tyrosine kinase (Src), which is involved in memory formation. Additionally, kinases that have not previously been associated with AD were identified, e.g., protein tyrosine kinase 6 (PTK6/BRK), feline sarcoma oncogene kinase (FES), and fyn-associated tyrosine kinase (FRK). The identified protein kinases are new biomarkers and potential drug targets for early (pre-clinical) intervention. | - |
dc.language.iso | en | - |
dc.rights | 2016 – IOS Press and the authors. All rights reserved This article is published online with Open Access and distributed under the terms of the Creative Commons Attribution Non-Commercial License. | - |
dc.subject.other | Alzheimer’s disease; peptide microarray analysis; phospho-peptides; postmortem changes; protein kinase activity; signaling pathways | - |
dc.title | Protein Kinase Activity Decreases with Higher Braak Stages of Alzheimers's Disease Pathology | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 943 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 927 | - |
dc.identifier.volume | 49 | - |
local.bibliographicCitation.jcat | A1 | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
local.class | dsPublValOverrule/internal_author_not_expected | - |
dc.identifier.doi | 10.3233/JAD-150429 | - |
dc.identifier.isi | 000367522800004 | - |
item.fulltext | With Fulltext | - |
item.accessRights | Open Access | - |
item.contributor | Rosenberger, Andrea F.N. | - |
item.contributor | Hilhorst, Riet | - |
item.contributor | Coart, Elisabeth | - |
item.contributor | GARCIA BARRADO, Leandro | - |
item.contributor | Naji, Faris | - |
item.contributor | Rozemuller, Annemieke J.M. | - |
item.contributor | Van der Flier, Wiesje M. | - |
item.contributor | Scheltens, Philip | - |
item.contributor | Hoozemans, Jeroen J.M. | - |
item.contributor | Van der Vies, Saskia M. | - |
item.fullcitation | Rosenberger, Andrea F.N.; Hilhorst, Riet; Coart, Elisabeth; GARCIA BARRADO, Leandro; Naji, Faris; Rozemuller, Annemieke J.M.; Van der Flier, Wiesje M.; Scheltens, Philip; Hoozemans, Jeroen J.M. & Van der Vies, Saskia M. (2016) Protein Kinase Activity Decreases with Higher Braak Stages of Alzheimers's Disease Pathology. In: Journal of Alzheimer's disease, 49(4), p. 927-943. | - |
crisitem.journal.issn | 1387-2877 | - |
crisitem.journal.eissn | 1875-8908 | - |
Appears in Collections: | Research publications |
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File | Description | Size | Format | |
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JAD150429.pdf | Published version | 833.55 kB | Adobe PDF | View/Open |
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