Selective aggregation of endogenous beta-amyloid peptide and soluble amyloid precursor protein in cerebrospinal fluid by zinc
| Autor: | Kenneth J. Rhodes, Donna M. Tummolo, John R. Hofmann, Abraham M. Brown, J. Steven Jacobsen, June Sonnenberg-Reines |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Pathology
medicine.medical_specialty Amyloid Blotting Western chemistry.chemical_element Peptide Enzyme-Linked Immunosorbent Assay Zinc Biochemistry Cellular and Molecular Neuroscience chemistry.chemical_compound Amyloid beta-Protein Precursor Dogs medicine Amyloid precursor protein Animals Humans Senile plaques Benzothiazoles Fluorescent Dyes chemistry.chemical_classification Amyloid beta-Peptides biology Chemistry P3 peptide Congo Red Congo red Thiazoles biology.protein Thioflavin |
| Zdroj: | Journal of neurochemistry. 69(3) |
| ISSN: | 0022-3042 |
| Popis: | Zinc added to buffered solutions of synthetic beta-amyloid peptide (A beta) has been reported to induce accelerated formation of insoluble aggregates. This observation suggests that zinc may play a role in the formation of senile plaques, which contain A beta, in Alzheimer's disease. To test this hypothesis under conditions more representative of the brain, we investigated the ability of zinc to induce aggregation of A beta in freshly drawn canine CSF, which contains the same sequence as human A beta. Aggregates were separated from CSF by ultracentrifugation before and after incubation with zinc and assayed by quantitative western blotting and ELISA. We found that zinc induced the rapid aggregation of endogenous A beta in CSF, with an EC50 of 120-140 microM. The reaction was specific, because most (> or = 95%) CSF protein remained soluble under conditions where most A beta was insoluble, as assayed by scanning densitometry of Coomassie-stained gels. Staining of the precipitated material resulted in the visualization of punctate regions that were thioflavin positive or birefringent when stained with Congo red, suggesting the formation of amyloid-related structures. These results suggest that zinc could play a role in amyloid deposition, because there is overlap between the regions of the brain where zinc concentrations are highest and regions with the highest amyloid content. It is surprising that zinc induced the aggregation of endogenous soluble APP at lower concentrations than required for A beta (EC50 80 microM). The possibility that zinc-induced aggregation of APP may precede the deposition of A beta into plaques is discussed. Investigation of aggregation of A beta in CSF will aid in assessing the biological relevance of other agents that have been reported to accelerate amyloid formation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text