Title: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
VOLUME: 16 ISSUE: 7
Author(s):Larry Schmued*, James Raymick and Sumit Sarkar
Affiliation:Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, 72079, Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, 72079, Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, AR, 72079
Keywords:Amyloid plaques, Alzheimer's disease, zinc chelator, brain pathology, Aβ, Amylo-Glo.
Abstract:
Background: 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.
Objective: This investigates 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, HQO,
was investigated to determine its mechanism of binding and to optimize a stain for the high contrast
and resolution histological localization of amyloid plaques.
Methods: A novel zinc chelator, HQ-O, was developed for localizing zinc within 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.
Results: 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.
Conclusion: 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.
