Étude de la relation entre les oligomères amyloïde-bêta et la protéine d'adhésion synaptique Neuroligine-1
Synaptic loss and neurodegeneration, partly induced by amyloid-beta oligomers (Aßo), are the best predictors of memory deficits in Alzheimer’s disease (AD). An actual priority in the field is to identify a novel biomarker affected early by Aßo. The post-synaptic protein Neuroligin-1 (NL-1) could be a good candidate due to its roles in synaptic plasticity and memory. The first hypothesis of this study is that the synaptic dysfunctions caused by Aβo could rapidly and gradually affect the level of NL1. NL-1 expression was measured in chronic hippocampal Aβo1-42 injections, in primary hippocampal neuronal cultures exposed to Aβo1-42, and in 3xTg mice. Using 5 sets of probes assessing Nl-1 transcripts, an increase in mRNA levels after 2 days of Aβo1-42 injections was detected for 2 sets of probes, and a decrease in 3 sets of probes expression were measured after 4 days of injections. However, no change in protein level was observed. In vitro, the level of NL-1 decreases after 72 hours of exposure to Aβo1-42, following the decrease in neuron viability. Finally, female 3xTg mice show a decrease in NL-1 at 4 months. In addition, the second hypothesis that the absence of NL-1 will lead to increased toxicity has been confirmed. Aβo1-42 injected NL-1 KO mice performed poorly in spatial object recognition and in the Morris water maze, and had greater neuronal loss than all the other groups tested. This study therefore confirms the close relationship between NL-1 and Aβo1-42, possibly providing a new therapeutic target or biomarker for the development of therapies in the early stages of AD.
Alzheimer’s disease Neuroligin-1 Amyloid-beta Memory Hippocampus