Title | Protein Kinase Activity Decreases with Higher Braak Stages of Alzheimer's Disease Pathology. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Rosenberger, AFN, Hilhorst, R, Coart, E, Barrado, LGarcĂa, Naji, F, Rozemuller, AJM, van der Flier, WM, Scheltens, P, Hoozemans, JJM, van der Vies, SM |
Journal | J Alzheimers Dis |
Volume | 49 |
Issue | 4 |
Pagination | 927-43 |
Date Published | 2016 |
ISSN | 1875-8908 |
Keywords | Aged, Aged, 80 and over, Alzheimer Disease, Cohort Studies, Female, Hippocampus, Humans, Male, Middle Aged, Phosphorylation, Protein Kinases, Protein-Serine-Threonine Kinases, Severity of Illness Index |
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 activity was determined in postmortem hippocampal brain tissue of 60 patients at various stages of AD and 40 non-demented 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 |
DOI | 10.3233/JAD-150429 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 26519433 |
PubMed Central ID | PMC4927853 |