Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Okamura, N. et al.

Quinoline and benzimidazole derivatives: candidate probes for in vivo imaging of tau pathology in Alzheimer's disease.

Neurofibrillary tangles (NFTs), neuropil threads, and neuritic elements of senile plaques predominantly comprise hyperphosphorylated tau protein and represent pathological characteristics of Alzheimer's disease (AD). These lesions occur before the presentation of clinical symptoms and correlate with the severity of dementia. In vivo detection of these lesions would thus prove useful for preclinical diagnosis of AD and for tracking disease progression. The present study introduces three novel compounds, 4-[2-(2-benzoimidazolyl)ethenyl]-N,N-diethylbenzenamine (BF-126), 2-[(4-methylamino)phenyl]quinoline (BF-158), and 2-(4-aminophenyl)quinoline (BF-170), as candidate probes for in vivo imaging of tau pathology in the AD brain. When solutions of these compounds are injected intravenously into normal mice, these agents exhibit excellent brain uptake and rapid clearance from normal brain tissue. These compounds display relatively lower binding affinity to beta-amyloid fibrils and higher binding affinity to tau fibrils, compared with previously reported probe BF-168. In neuropathological examination using AD brain sections, BF-126, BF-158, and BF-170 clearly visualize NFTs, neuropil threads, and paired helical filament-type neuritis. Autoradiography using 11C-labeled BF-158 further demonstrated labeling of NFTs in AD brain sections. These findings suggest the potential usefulness of quinoline and benzimidazole derivatives for in vivo imaging of tau pathology in AD.[1]

References

Quinoline and benzimidazole derivatives: candidate probes for in vivo imaging of tau pathology in Alzheimer's disease. Okamura, N., Suemoto, T., Furumoto, S., Suzuki, M., Shimadzu, H., Akatsu, H., Yamamoto, T., Fujiwara, H., Nemoto, M., Maruyama, M., Arai, H., Yanai, K., Sawada, T., Kudo, Y. J. Neurosci. (2005) [Pubmed]

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