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PMID: 17928437 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer's disease enabled by positron emission tomography.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 27 ·No. 41 ·2007-10-10 ·Pages 10957-68

Maeda J, Ji B, Irie T, Tomiyama T, Maruyama M, Okauchi T, Staufenbiel M, Iwata N, Ono M, Saido TC, Suzuki K, Mori H, Higuchi M, Suhara T

Abstract

We provide the first evidence for the capability of a high-resolution positron emission tomographic (PET) imaging system in quantitatively mapping amyloid accumulation in living amyloid precursor protein transgenic (Tg) mice. After the intravenous administration of N-[11C]methyl-2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (or [11C]PIB for "Pittsburgh Compound-B") with high-specific radioactivity, the Tg mice exhibited high-level retention of radioactivity in amyloid-rich regions. PET investigation for Tg mice over an extended range of ages, including longitudinal assessments, demonstrated age-dependent increase in radioligand binding consistent with progressive amyloid accumulation. Reduction in amyloid levels in the hippocampus of Tg mice was also successfully monitored by multiple PET scans along the time course of anti-amyloid treatment using an antibody against amyloid beta peptide (Abeta). Moreover, PET scans with [18F]fluoroethyl-DAA1106, a radiotracer for activated glia, were conducted for these individuals parallel to amyloid imaging, revealing treatment-induced neuroinflammatory responses, the magnitude of which intimately correlated with the levels of pre-existing amyloid estimated by [11C]PIB. It is also noteworthy that the localization and abundance of [11C]PIB autoradiographic signals were closely associated with those of N-terminally truncated and modified Abeta, AbetaN3-pyroglutamate, in Alzheimer's disease (AD) and Tg mouse brains, implying that the detectability of amyloid by [11C]PIB positron emission tomography is dependent on the accumulation of specific Abeta subtypes. Our results support the usefulness of the small animal-dedicated PET system in conjunction with high-specific radioactivity probes and appropriate Tg models not only for clarifying the mechanistic properties of amyloidogenesis in mouse models but also for preclinical tests of emerging diagnostic and therapeutic approaches to AD.

MeSH Terms
Age Factors Alzheimer Disease/diagnostic imaging,pathology,therapy Amyloid beta-Peptides/antagonists & inhibitors,genetics,immunology Aniline Compounds Animals Antibodies/therapeutic use Disease Models, Animal Female Inflammation/diagnostic imaging,pathology,therapy Longitudinal Studies Mice Mice, Inbred C57BL Mice, Transgenic Neurofibrillary Tangles/diagnostic imaging,pathology Positron-Emission Tomography/methods Thiazoles
Chemicals
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole Amyloid beta-Peptides Aniline Compounds Antibodies Thiazoles
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Maeda Jun
Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Chiba 263-8555, Japan.
Ji Bin
Irie Toshiaki
Tomiyama Takami
Maruyama Masahiro
Okauchi Takashi
Staufenbiel Matthias
Iwata Nobuhisa
Ono Maiko
Saido Takaomi C
Suzuki Kazutoshi
Mori Hiroshi
Higuchi Makoto
Suhara Tetsuya
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.0673-07.2007
Published
2007-10-10
Pages
10957-68
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6672864
Subset
IM
External Links
PubMed source DOI: 10.1523/JNEUROSCI.0673-07.2007 PMC Full Text View journal details
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