Shamsideen Ojelade, United States of America
Baylor College of Medicine NeurologyAuthor Of 1 Presentation
THE ALZHEIMER'S DISEASE RISK GENE CD2AP MODULATES MAMMALIAN SYNAPTIC STRUCTURE AND PLASTICITY
Abstract
Aims
CD2-Associated protein (CD2AP) is associated with an increased risk of late-onset Alzheimer’s disease (AD). We previously show that loss of CD2AP’s Drosophila homolog, cindr, exacerbates Tau toxicity and impairs synaptic maturation and short-term plasticity in flies. However, little is understood about CD2AP’s role at the central mammalian synapse. The present study investigates CD2AP’s role at the post-synapse and in long-term plasticity.
Methods
Using a CD2AP knockout mouse (CD2AP-/-), we examined short- and long-term plasticity via electrophysiological recordings and assessed morphological changes in primary neuronal cultures. Since CD2AP-/- mice die within 6-7 weeks of age, CD2AP heterozygous mice were also examined.
Results
CD2AP is expressed ubiquitously in the brain and enriched at the mouse hippocampus. Using hippocampal slice electrophysiology, we show that both heterozygous and homozygous CD2AP knockouts mice exhibit enhanced paired-pulse facilitation when compared to controls. Although tetanic stimulation performed in young (4-6 weeks old) mice shows inductions of long-term potentiation (LTP) similar to that seen in controls, we observed decreased LTP in aged CD2AP heterozygous mice. In cell culture, CD2AP-/- neurons exhibit increased dendritic branching and PSD95 expression when compared to controls suggesting that CD2AP regulates post-synaptic structure and function.
Conclusions
Taken together, our study shows conserved function of CD2AP for short-term plasticity in flies and mice and suggest haploinsufficient requirements of CD2AP for LTP in an age-dependent manner. Ongoing research will further characterize CD2AP at the post-synapse and in a tauopathy model of AD.