12 research outputs found
siRNA targeted against amyloid precursor protein impairs synaptic activity in vivo
International audienceThe amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD) pathogenesis through its cleavage leading to the accumulation of the peptide A4. Diffusible oligomeric assemblies of amyloid beta peptide are thought to induce synaptic dysfunction, an early change in AD. We tested the hypothesis that a reduction in presynaptic APP could itself lead to a decrease in synaptic efficacy in vivo. Twenty-four hours after intraocular injection, siRNA targeted against APP accumulated in retinal cells and the APP in retinal terminals in the superior colliculus was significantly reduced. Surprisingly, the amyloid precursor-like protein 2 (APLP2) was reduced as well. Functional imaging experiments in rats during visual stimulation showed that knockdown of presynaptic APP/APLP2 significantly reduced the stimulation-induced glucose utilization in the superior colliculus. Our results suggest that perturbations in the amount of APP/APLP2 axonally transported to, and/or in their turnover in the nerve terminal alter synaptic function and could be a pathogenic mechanism in AD
3'-Deoxy-3'-[(18)F]Fluorothymidine uptake is related to thymidine phosphorylase expression in various experimental tumor models
PURPOSE: We recently reported that high thymidine phosphorylase (TP) expression is accompanied by low tumor thymidine concentration and high 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake in four untreated lung cancer xenografts. Here, we investigated whether this relationship also holds true for a broader range of tumor models. PROCEDURES: Lysates from n = 15 different tumor models originating from n = 6 institutions were tested for TP and thymidylate synthase (TS) expression using western blots. Results were correlated to [(18)F]FLT accumulation in the tumors as determined by positron emission tomography (PET) measurements in the different institutions and to previously published thymidine concentrations. RESULTS: Expression of TP correlated positively with [(18)F]FLT SUVmax (ρ = 0.549, P < 0.05). Furthermore, tumors with high TP levels possessed lower levels of thymidine (ρ = - 0.939, P < 0.001). CONCLUSIONS: In a broad range of tumors, [(18)F]FLT uptake as measured by PET is substantially influenced by TP expression and tumor thymidine concentrations. These data strengthen the role of TP as factor confounding [(18)F]FLT uptake