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Evaluation of 18F-nifrolene binding to transgenic mice model of Alzheimer’s disease

¹ University of California of Irvine, Irvine, California

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Objectives: Agonists have shown that nicotinic 4β2 receptors are reduced in the cortex, hippocampus and thalamus in Alzheimer’s disease (AD) and in transgenic mice models of AD. We now report on the binding of the antagonist, 18F-nifrolene in transgenic mouse model of AD (Tg2576 for β-amyloid plaques).

Methods: 18F-Nifrolene was prepared as reported. Whole brain sagittal sections (10 µm thick) were obtained from the Tg mice and wild-type (WT) mice. Brain sections were treated with 18F-nifrolene with concentrations ~2µCi/cc. The sections were incubated for 60 min at 37°C, washed (2x2 min cold buffer, water), dried and exposed to phosphor screens. Nonspecific binding was measured in the presence of 300µM of nicotine. Binding was determined by autoradiograms analyzed by OptiQuant Image Analysis Software. Adjacent mice brain sections were also immunostained with anti-Aβ antibody and thioflavin to confirm presence of β-amyloid plaques and 4β2 antibody for the receptor.

Results: Ratios of thalamus (TH) and cortex (CO) to cerebellum (CE) in the wild type (WT) were TH/CE=12 and TH/CO=2.2. The 15 mo old transgenic mice brains displayed significant loss of 18F-nifrolene with TH/CE=1.1 and CO/CE=1.47. In the presence of nicotine, WT ratios were TH/CE=0.7 and CO/CE=0.6 and Tg2576 were TH/CE=1.15 and CO/CE=1.52. The significant cortical binding observed in Tg2576 was not displaced by nicotine. Anti-Aβ antibody immunostain suggests the presence of plaques in the cortical regions with 18F-nifrolene binding.

Conclusions: Significant loss of 18F-nifrolene binding may be due to alteration of 4β2 receptors by β-amyloid plaques. 4β2 activity is localized in AD brains to β plaques and neurofibrillary tangles (Sparks et al., 1998). The characteristics of 18F-nifrolene that prevent displacement by nicotine are being investigated.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Patel, N. Articles by Mukherjee, J. PubMed Articles by Patel, N. Articles by Mukherjee, J.