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High contrast and resolution labeling of amyloid plaques in tissue sections from APP-PS1 mice and humans with Alzheimer's Disease with the zinc chelator HQ-O: Practical and theoretical considerations.

  • Schmued, Larry1
  • Raymick, James1
  • Sarkar, Sumit1
  • 1 Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, 72079. United States. , (United States)
Published Article
Current Alzheimer research
Publication Date
Jul 25, 2019
DOI: 10.2174/1567205016666190725155038
PMID: 31345150


Various methodologies have been employed for the localization of amyloid plaques in numerous studies on Alzheimer's disease. The majority of these stains are thought to label the plaques by virtue of their affinity for aggregated Aβ. However, plaques are known to contain numerous other components, including multivalent metals such as zinc. To investigate whether it is possible to localize the presence of zinc in parenchymal and vascular amyloid plaques in afflicted brains. To accomplish this, a novel fluorescent zinc chelator, HQ-O, was investigated to determine its mechanism of binding and to optimize a stain for the high contrast and resolution histological localization of amyloid plaques. A novel zinc chelator, HQ-O, was developed for localizing zinc containing amyloid plaques. The histology involves incubating tissue sections in a dilute aqueous solution of HQ-O. Its compatibility with a variety of other fluorescent methodologies is described. All amyloid plaques are stained in fine detail and appear bright green under blue light excitation. The staining of parenchymal plaques correlates closely with that seen following staining with antibodies to Aβ, however, the HQ-O sometimes also label additional globular structures within blood vessels. In situ mechanistic studies revealed that fluorescent plaque-like structures are only observed with HQ-O when synthetic Aβx-42 is aggregated in the presence of zinc. Zinc is intimately bound to all amyloid plaques, which was demonstrated by its histological localization using a novel fluorescent zinc chelator, HQ-O. Additionally, the tracer is also capable of labeling intravascular leucocytes due to their high zinc content. Copyright© Bentham Science Publishers; For any queries, please email at [email protected]

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