Evaluation of Styrylbenzene analog- FSB and its affinity to bind parenchymal plaques and tangles in patients of Alzheimer's disease.


Journal

Metabolic brain disease
ISSN: 1573-7365
Titre abrégé: Metab Brain Dis
Pays: United States
ID NLM: 8610370

Informations de publication

Date de publication:
03 2022
Historique:
received: 05 08 2021
accepted: 05 12 2021
pubmed: 23 1 2022
medline: 8 4 2022
entrez: 22 1 2022
Statut: ppublish

Résumé

Although several histochemical markers for senile plaques (SP) and neurofibrillary tangles (NFTs) have been synthesized since the discovery of plaques in Alzheimer's disease (AD), only a handful of these markers stain both lesions in the human brain. Despite discovery of its ability to stain both SP and NFT over 13 years ago, the styrylbenzene derivative, (E,E)-1-fluoro-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (FSB), has only recently gained attention, primarily due to its ability to function as a contrasting agent for MRI imaging of AD pathology in vivo. The structure of the compound is a nuclide with quantized angular momentum, which explains its value as a contrast agent. In the current study, modification of the established staining procedure produced meaningful improvement in the labeling of plaques and tangles in the human brain. We utilized two rodent models of AD to show FSB's value in labeling both Aβ and tau lesions. Furthermore, our current modification allows us to detect SP in rodent brains in 15 min and both SP and NFT in human brains within 20 min. The study presents new evidence regarding potential binding targets for FSB as well as optimization protocols in which various parameters have been manipulated to show how section thickness, use of frozen versus paraffin-embedded sections, and selection of staining media can affect the intensity of the plaque and tangle staining in the brain. To determine the target FSB potentially binds, we performed double immunolabeling of FSB with mOC64 (a conformational antibody that label Aβ

Identifiants

pubmed: 35064472
doi: 10.1007/s11011-021-00885-3
pii: 10.1007/s11011-021-00885-3
doi:

Substances chimiques

Amyloid beta-Peptides 0
tau Proteins 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

639-651

Informations de copyright

© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Références

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Auteurs

Sharay E Setti (SE)

Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Rd., Jefferson, AR, 72079, USA.

Nikita Das (N)

Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Rd., Jefferson, AR, 72079, USA.

James Raymick (J)

Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Rd., Jefferson, AR, 72079, USA.

Joseph Hanig (J)

Office of Regulatory Affairs, Office of Regulatory Science, Food and Drug Administration, Rockville, MD, USA.

Sumit Sarkar (S)

Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Rd., Jefferson, AR, 72079, USA. Sumit.Sarkar@FDA.HHS.GOV.

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Classifications MeSH