PIB binding in aged primate brain: Enrichment of high-affinity sites in humans with Alzheimer's disease

Rebecca F. Rosen; Lary C. Walker; Harry LeVine

doi:10.1016/j.neurobiolaging.2009.02.011

PIB binding in aged primate brain: Enrichment of high-affinity sites in humans with Alzheimer's disease

Rebecca F. Rosen, Lary C. Walker, Harry LeVine

Molecular and Cellular Biochemistry

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

Abstract

Aged nonhuman primates accumulate large amounts of human-sequence amyloid β (Aβ) in the brain, yet they do not manifest the full phenotype of Alzheimer's disease (AD). To assess the biophysical properties of Aβ that might govern its pathogenic potential in humans and nonhuman primates, we incubated the benzothiazole imaging agent Pittsburgh Compound B (PIB) with cortical tissue homogenates from normal aged humans, humans with AD, and from aged squirrel monkeys, rhesus monkeys, and chimpanzees with cerebral Aβ-amyloidosis. Relative to humans with AD, high-affinity PIB binding is markedly reduced in cortical extracts from aged nonhuman primates containing levels of insoluble Aβ similar to those in AD. The high-affinity binding of PIB may be selective for a pathologic, human-specific conformation of multimeric Aβ, and thus could be a useful experimental tool for clarifying the unique predisposition of humans to Alzheimer's disease.

Original language	English
Pages (from-to)	223-234
Number of pages	12
Journal	Neurobiology of Aging
Volume	32
Issue number	2
DOIs	https://doi.org/10.1016/j.neurobiolaging.2009.02.011
State	Published - Feb 2011

Bibliographical note

Funding Information:
We thank Brian Ciliax, M. Paul Murphy and Jorge Ghiso for helpful discussions and technical expertise, Marla Gearing, Todd Preuss, Mary Lou Voytko, Amy Arnsten, Douglas Rosene and Daniel Anderson for generously providing tissue, and Jeromy Dooyema, Aaron Farberg and Carolyn Suwyn for excellent technical assistance. Funding was provided by the University Research Committee of Emory University, RR-00165, PO1AG026423, P50AG025688 and the Woodruff Foundation.

Funding

We thank Brian Ciliax, M. Paul Murphy and Jorge Ghiso for helpful discussions and technical expertise, Marla Gearing, Todd Preuss, Mary Lou Voytko, Amy Arnsten, Douglas Rosene and Daniel Anderson for generously providing tissue, and Jeromy Dooyema, Aaron Farberg and Carolyn Suwyn for excellent technical assistance. Funding was provided by the University Research Committee of Emory University, RR-00165, PO1AG026423, P50AG025688 and the Woodruff Foundation.

Funders	Funder number
University Research Committee, Emory University	RR-00165, PO1AG026423
National Institute on Aging	P50AG025688
Woodruff Foundation

Keywords

Alzheimer's disease
Aβ
Benzothiazole
Cerebral amyloid angiopathy
Imaging
Nonhuman primates
Pittsburgh Compound B
Senile plaques
β-Amyloid

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.neurobiolaging.2009.02.011

Cite this

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title = "PIB binding in aged primate brain: Enrichment of high-affinity sites in humans with Alzheimer's disease",

abstract = "Aged nonhuman primates accumulate large amounts of human-sequence amyloid β (Aβ) in the brain, yet they do not manifest the full phenotype of Alzheimer's disease (AD). To assess the biophysical properties of Aβ that might govern its pathogenic potential in humans and nonhuman primates, we incubated the benzothiazole imaging agent Pittsburgh Compound B (PIB) with cortical tissue homogenates from normal aged humans, humans with AD, and from aged squirrel monkeys, rhesus monkeys, and chimpanzees with cerebral Aβ-amyloidosis. Relative to humans with AD, high-affinity PIB binding is markedly reduced in cortical extracts from aged nonhuman primates containing levels of insoluble Aβ similar to those in AD. The high-affinity binding of PIB may be selective for a pathologic, human-specific conformation of multimeric Aβ, and thus could be a useful experimental tool for clarifying the unique predisposition of humans to Alzheimer's disease.",

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note = "Funding Information: We thank Brian Ciliax, M. Paul Murphy and Jorge Ghiso for helpful discussions and technical expertise, Marla Gearing, Todd Preuss, Mary Lou Voytko, Amy Arnsten, Douglas Rosene and Daniel Anderson for generously providing tissue, and Jeromy Dooyema, Aaron Farberg and Carolyn Suwyn for excellent technical assistance. Funding was provided by the University Research Committee of Emory University, RR-00165, PO1AG026423, P50AG025688 and the Woodruff Foundation. ",

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doi = "10.1016/j.neurobiolaging.2009.02.011",

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PIB binding in aged primate brain: Enrichment of high-affinity sites in humans with Alzheimer's disease

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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