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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 accessAbstract
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-[11 C]methyl-2-(4′-methylaminophenyl)-6-hydroxybenzothiazole (or [11 C]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 [18 F]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 [11 C]PIB. It is also noteworthy that the localization and abundance of [11 C]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 [11 C]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.
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“interestingly vascular amyloid is somewhat different in its composition 79 and potentially, its conformation from the parenchymal Aβ plaques 92 .”
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Metadata
- Authors
- Maeda, J., Ji, B., Irie, T., Tomiyama, T., Maruyama, M., Okauchi, T., Staufenbiel, M., Iwata, N., Ono, M., Saido, T. C., Suzuki, K., Mori, H., Higuchi, M., & Suhara, T.
- Affiliations
- National Institute of Radiological Sciences (JP)
- Osaka City University (JP)
- Novartis (Switzerland) (CH)
- RIKEN Center for Brain Science (JP)
- Corresponding author
- Higuchi, Makoto
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-10-10
- Volume
- 27
- Issue
- 41
- Pages
- 10957-10968
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6672864
- OpenAlex
- W1984320700
- Cited by
- 300
- References
- 45
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 2 · 2022: 8 · 2021: 10 · 2020: 18 · 2019: 5 · 2018: 8 · 2017: 10 · 2016: 12 · 2015: 15 · 2014: 21 · 2013: 23 · 2012: 38
- FWCI
- 20.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (18023033, 18023040)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid imaging, Pittsburgh compound B, [11C]PIB, amyloid precursor protein transgenic mice, neuroinflammation, amyloid-beta, amyloid accumulation, hippocampus, longitudinal imaging
- MeSH terms
- Age Factors, Alzheimer Disease, Aniline Compounds, Animals, Antibodies, Disease Models, Animal, Female, Inflammation, Longitudinal Studies, Mice, Inbred C57BL, Mice, Transgenic, Thiazoles, Amyloid beta-Peptides, Neurofibrillary Tangles, Positron-Emission Tomography, Mice
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