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Copper accumulation and the effect of chelation treatment on cerebral amyloid angiopathy compared to parenchymal amyloid plaques

Journal Article · · Metallomics
DOI:https://doi.org/10.1039/c9mt00306a· OSTI ID:1646572
 [1];  [2];  [3];  [1];  [1];  [1];  [3];  [1]
  1. Univ. of Rhode Island, Kingston, RI (United States)
  2. Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)
  3. Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II); Stony Brook Univ., NY (United States)
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Accumulation of fibrillar amyloid b-protein (Ab) 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. In this work 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.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS); Brookhaven National Laboratory (BNL), Upton, NY (United States). National Synchrotron Light Source II (NSLS-II)
Sponsoring Organization:
National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Grant/Contract Number:
AC02-06CH11357; SC0012704
OSTI ID:
1646572
Alternate ID(s):
OSTI ID: 1632899
Report Number(s):
BNL--216227-2020-JAAM
Journal Information:
Metallomics, Journal Name: Metallomics Journal Issue: 4 Vol. 12; ISSN 1756-5901
Publisher:
Royal Society of ChemistryCopyright Statement
Country of Publication:
United States
Language:
English

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