Copper accumulation and the effect of chelation treatment on cerebral amyloid angiopathy compared to parenchymal amyloid plaques
| Autor: | Joseph K. Sullivan, Xiayoue Zhu, Ashwin Ambi, Tiffany W Victor, Lisa M. Miller, Joshua Hatfield, Feng Xu, William E. Van Nostrand |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Amyloid Biophysics chemistry.chemical_element Mice Transgenic Plaque Amyloid Biochemistry Article Biomaterials 03 medical and health sciences 0302 clinical medicine Alzheimer Disease Parenchyma mental disorders medicine Animals Humans Chelation Copper levels Parenchymal Tissue Chelating Agents Molybdenum Amyloid beta-Peptides Chemistry Metals and Alloys Brain Copper Chelation medicine.disease Copper Copper Chelator Cerebral Amyloid Angiopathy Disease Models Animal 030104 developmental biology Microscopy Fluorescence Chemistry (miscellaneous) Cerebral amyloid angiopathy 030217 neurology & neurosurgery |
| Zdroj: | Metallomics |
| ISSN: | 1756-591X |
| Popis: | Accumulation of fibrillar amyloid β-protein (Aβ) in parenchymal plaques and in blood vessels of the brain, the latter condition known as cerebral amyloid angiopathy (CAA), are hallmark pathologies of Alzheimer’s disease (AD) and related disorders. Cerebral amyloid deposits have been reported to accumulate various metals, most notably copper and zinc. Here we show that, in human AD, copper is preferentially accumulated in amyloid-containing brain blood vessels compared to parenchymal amyloid plaques. In light of this observation, we evaluated the effects of reducing copper levels in Tg2576 mice, a transgenic model of AD amyloid pathologies. The copper chelator, tetrathiomolybdate (TTM), was administered to twelve month old Tg2576 mice for a period of five months. Copper chelation treatment significantly reduced both CAA and parenchymal plaque load in Tg2576 mice. Further, copper chelation reduced parenchymal plaque copper content but had no effect on CAA copper levels in this model. These findings indicate that copper is associated with both CAA deposits and parenchymal amyloid plaques in humans, but less in Tg2576 mice. TTM only reduces copper levels in plaques in Tg2576 mice. Reducing copper levels in the brain may beneficially lower amyloid pathologies associated with AD. |
| Databáze: | OpenAIRE |
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