According to the Alzheimer's Association, one of the world's epidemics is Alzheimer's disease, afflicting an estimated 50 million people globally and 5.8 million in the U.S. With the aging of the Baby Boomer generation, the prevalence of the debilitating condition is expected to increase dramatically in the coming years. Currently, no treatment exists to prevent, reverse, or halt the progression of Alzheimer's disease, and new medications may only relieve dementia symptoms for a short time.
A significant genetic risk factor for the development of Alzheimer's disease is Apolipoprotein E (apoE), yet the protein tends to be understudied as a potential druggable target for the mind-robbing neurodegenerative disease.
Recently, a group of researchers led by the University of South Florida Health (USF Health) Morsani College of Medicine report that a new apoE antagonist blocks apoE interaction with N-terminal amyloid precursor protein (APP). They published the preclinical study in Biological Psychiatry.
Furthermore, the 6KApoEp, also known as peptide antagonist, was shown to reduce Alzheimer's-associated beta-amyloid (β-amyloid) accumulation and tau pathologies in the brain, as well as improving learning and memory in mice genetically engineered to mimic symptoms of Alzheimer's disease.
Researchers have directed many failed anti-amyloid therapies for Alzheimer's disease against various forms of the protein β-amyloid, which ultimately forms clumps of sticky plaques in the brain. The presence of these amyloid plaques is one of the main hallmarks of Alzheimer's disease.
The findings of the USF Health study suggests that disrupting apoE physical interaction with the N-terminal APP may be a new disease-modifying therapeutic strategy for this most common type of dementia.
The study's lead author and an assistant professor in the USF Health Department of Psychiatry & Behavioral Neurosciences, Darrell Sawmiller, said that for the first time, scientists have direct evidence that the N-terminal section of apoE itself acts as an essential molecule (ligand) to promote the binding of apoE to the N-terminal region of APP outside the nerve cells. This receptor-mediated mechanism plays a role in the development of Alzheimer's disease. Overstimulation of APP by apoE may be an earlier, upstream event that signals other neurodegenerative processes contributing to the amyloid cascade.
Jun Tan, Ph.D., MD, a professor in the USF Health Department of Psychiatry & Behavioral Neuroscience, the senior author of the study, said that initially, they wanted to understand better how apoE pathologically interacts with APP, which leads to the formation of β-amyloid plaques and neuronal loss. Tan noted further that their work discovered an apoE derivative that can modulate structural and functional neuropathology in Alzheimer's disease mouse models.
