Longitudinal, Quantitative Assessment of Amyloid, Neuroinflammation, and Anti-Amyloid Treatment in a Living Mouse Model of Alzheimer's Disease Enabled by Positron Emission Tomography
作者： J. Maeda , B. Ji , T. Irie , T. Tomiyama , M. Maruyama
DOI: 10.1523/JNEUROSCI.0673-07.2007
关键词:
摘要: We provide the first evidence for capability of a high-resolution positron emission tomographic (PET) imaging system in quantitatively mapping amyloid accumulation living precursor protein transgenic (Tg) mice. After intravenous administration N-[11C]methyl-2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (or [11C]PIB "Pittsburgh Compound-B") with high-specific radioactivity, Tg mice exhibited high-level retention radioactivity amyloid-rich regions. PET investigation over an extended range ages, including longitudinal assessments, demonstrated age-dependent increase radioligand binding consistent progressive accumulation. Reduction levels hippocampus was also successfully monitored by multiple scans along time course anti-amyloid treatment using antibody against beta peptide (Abeta). Moreover, [18F]fluoroethyl-DAA1106, radiotracer activated glia, were conducted these individuals parallel to imaging, revealing treatment-induced neuroinflammatory responses, magnitude which intimately correlated pre-existing estimated [11C]PIB. It is noteworthy that localization and abundance autoradiographic signals closely associated those N-terminally truncated modified Abeta, AbetaN3-pyroglutamate, Alzheimer's disease (AD) mouse brains, implying detectability tomography dependent on specific Abeta subtypes. Our results support usefulness small animal-dedicated conjunction probes appropriate models not only clarifying mechanistic properties amyloidogenesis but preclinical tests emerging diagnostic therapeutic approaches AD.
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