CD40 ligation mediates plaque-associated tau phosphorylation in beta-amyloid overproducing mice
| Autor: | Marcie Wood, Christopher Ganey, Nowell J. Ganey, Michael Mullan, Ghania Ait-Ghezala, Claude-Henry Volmar, Vincent Laporte |
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| Rok vydání: | 2007 |
| Předmět: |
Genetically modified mouse
Pathology medicine.medical_specialty Neurite Amyloid Transgene Tau protein CD40 Ligand Down-Regulation Plaque Amyloid tau Proteins Amyloid beta-Protein Precursor Mice Alzheimer Disease Cell Line Tumor mental disorders medicine Neurites Animals Humans CD40 Antigens Phosphorylation Coloring Agents Molecular Biology Mice Knockout Amyloid beta-Peptides biology General Neuroscience Phosphotransferases Brain hemic and immune systems Congo Red Cyclin-Dependent Kinase 5 Neurofibrillary Tangles medicine.disease Biochemistry of Alzheimer's disease Mice Inbred C57BL Disease Models Animal nervous system Chromobox Protein Homolog 5 biology.protein Neurology (clinical) Astrocytosis Alzheimer's disease Developmental Biology |
| Zdroj: | Brain research. 1231 |
| ISSN: | 0006-8993 |
| Popis: | Neuritic dystrophy with amyloid burden and neurofibrillary tangles are pathological hallmarks of Alzheimer's disease. Genetic disruption of CD40 or CD40L alleviates amyloid burden, astrocytosis, and microgliosis in transgenic animal models of Alzheimer's disease. It has been reported that phosphorylated tau-positive dystrophic neurites are observed in transgenic mice over-expressing human mutant beta-amyloid precursor protein (Tg2576). Here, we studied the pattern of phosphorylated tau (labeled with AT8, CP13, PG5, and PHF1 antibodies) and plaques using immunohistochemical techniques. Phosphorylated tau-positive dystrophic neurites were exclusively associated with Congo red-positive plaques as previously reported. Further, we show that CD40L or CD40 deficiency reduces the mean ratio of dystrophic neurite area to congophilic plaque area and the level of expression of cdk5 and p35/p25 in mice. In addition, we show that in a human neuroblastoma cell line treated with CD40L, cdk5 and p35/p25 are increased. Together, our data suggest that CD40–CD40L interaction has an effect on tau phosphorylation independent of beta-amyloid pathology, and that this effect may occur through a decrease of cdk5 and p35/p25. |
| Databáze: | OpenAIRE |
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