We are glad to share our first bioRxiv preprint in 2024.
Alzheimer’s disease is characterized by cognitive decline and memory loss, and genetic variations in humans are key to understanding it. Our study focused on the ABCA7 gene, which is linked to Alzheimer’s risk. We used CRISPR/Cas9 gene editing to create zebrafish with a genetic alteration similar to that found in humans. We then examined the zebrafish for changes in neuronal connectivity. We discovered that gene-edited zebrafish led to a decrease in certain brain activities and proteins, including Neuropeptide Y (Npy) and brain derived neurotrophic factor (Bdnf) essential for maintaining brain cell connections and resilience. By analyzing clinical human data, we confirmed the importance of this new ABCA7-dependent signaling mechanism in Alzheimer’s. Our study concludes that ABCA7-dependent genetic pathway is crucial for brain resilience and synaptic integrity, offering insights into potential treatments for Alzheimer’s.
This study was supported by various grants including NIH, NIA, NINDS, Alzheimer’s Association, Columbia University Irving Medical Center, Mayo Clinic, Taub Institute for Research on Alzheimer’s disease and the Aging Brain, Schaefer Family Scholars Award, Carol and Gene Ludwig Foundation, and Thompson Family Foundation.
Congratulations to all authors!
Kizil Lab 