Sep 3, 2024 Story by: Editor
Researchers at Columbia University have uncovered how variations in the ABCA7 gene, which are prevalent among Black Americans, heighten the risk of developing Alzheimer’s disease. These genetic variants accelerate neurodegeneration by diminishing levels of neuropeptide Y, a crucial protein for maintaining synapses in the brain and ensuring the resilience of neurons.
“Our findings not only enhance our understanding of Alzheimer’s, but they also provide a new direction for developing treatments that could halt or reverse the progression of the disease,” stated Caghan Kizil, PhD, the study’s lead author and an associate professor of neurological sciences at Columbia University Vagelos College of Physicians and Surgeons, as well as the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain.
Importance of the Discovery
About ten years ago, variants in the ABCA7 gene were first associated with an increased risk of Alzheimer’s disease, but the mechanisms behind how these variants contribute to disease progression remained unclear. While ABCA7 variants have been linked to a higher risk of Alzheimer’s across various racial and ethnic groups, they are especially significant among Black Americans. In fact, ABCA7 variants have a stronger correlation with Alzheimer’s in Black Americans than the widely recognized APOE4 gene, which is the most influential Alzheimer’s gene in white Americans.
Understanding the molecular mechanisms behind genetic risk factors like ABCA7 is essential for developing new therapeutic drugs.
Utilizing Zebrafish for Research
In their study, Kizil and his team removed one copy of the ABCA7 gene in zebrafish neurons, simulating the gene’s disruption seen in humans. The zebrafish model allows researchers to gather information about Alzheimer’s variants much faster than traditional animal models, which can take months or even years.
The findings revealed that the loss of one ABCA7 copy resulted in decreased neuropeptide Y expression across all brain regions, with the most significant reduction occurring in the hippocampus, the region responsible for memory.
“This disruption in neuropeptide Y levels impaired neurogenesis and reduced synaptic density, both of which are key factors in Alzheimer’s pathology,” Kizil explained.
In human cells, the researchers observed a similar process in neurons derived from pluripotent stem cells and found indications that the neuropeptide Y pathway is compromised in the brains of individuals with Alzheimer’s.
Moreover, the researchers successfully restored synaptic integrity in zebrafish by replenishing neuropeptide Y or other components within its pathway, pointing to a potential therapeutic target for Alzheimer’s disease. Source: CUIMC
