Longitudinal, Quantitative Assessment of Amyloid, Neuroinflammation, and Anti-Amyloid Treatment in a Living Mouse Model of Alzheimer's Disease Enabled by Positron Emission Tomography
Open Access
- 10 October 2007
- journal article
- research article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 27 (41), 10957-10968
- https://doi.org/10.1523/jneurosci.0673-07.2007
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 ofN-[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 β peptide (Aβ). 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 Aβ, AβN3-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 Aβ 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.Keywords
This publication has 41 references indexed in Scilit:
- Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse ModelNeuron, 2007
- PET imaging of transgenic mice TG2576 using the beta-amyloid radioligand, [C-11]PIBNeuroImage, 2006
- In vivo detection of amyloid-β deposits by near-infrared imaging using an oxazine-derivative probeNature Biotechnology, 2005
- Fluoro-substituted and 13C-labeled styrylbenzene derivatives for detecting brain amyloid plaquesEuropean Journal of Medicinal Chemistry, 2004
- Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐BAnnals of Neurology, 2004
- Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic MiceScience, 1996
- Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1Nature, 1996
- Comparison of Methods for Analysis of Clinical [11C]Raclopride StudiesJournal of Cerebral Blood Flow & Metabolism, 1996
- Dominant and differential deposition of distinct β-amyloid peptide species, AβN3(pE), in senile plaquesNeuron, 1995
- Computer-controlled large scale production of high specific activity [11C]RO 15-1788 for PET studies of benzodiazepine receptorsThe International Journal of Applied Radiation and Isotopes, 1985