NIH Awards $4.8M Grant to Project Investigating the Role of ApoE4 Gene Variant in Alzheimer’s

NIH Awards $4.8M Grant to Project Investigating the Role of ApoE4 Gene Variant in Alzheimer’s
The National Institutes of Health (NIH) has awarded a $4.8-million grant to support a project designed to discover how the ApoE4 gene variant, a known genetic risk factor for late-onset Alzheimer's disease, induces neurodegeneration. The apolipoprotein E (ApoE) proteins encoded by the APOE gene help in the repair of nerve cells (neurons) upon damage caused by aging or a stroke, among others. The three forms of ApoE proteins are ApoE2, ApoE3, and ApoE4, each encoded by a different APOE allele (different versions of the same gene). ApoE2 is the rarest form and is considered neuroprotective, while ApoE3 is the most common form. ApoE4 is found in approximately 25% of the human population and in two-thirds of those with Alzheimer’s. Despite being similar, ApoE3 and ApoE4 have different shapes. The structure of ApoE4 increases the likelihood that it'll break down into smaller toxic fragments inside neurons. Scientists believe these toxic fragments may change key processes taking place inside neurons, culminating in their death. “ApoE4 dramatically rewires cellular pathways in neurons and impairs their function," Robert Mahley, MD, PhD, a senior researcher at Gladstone Institutes, and the project’s lead researcher, said in a
Subscribe or to access all post and page content.