Animal Model Mimics Early Stage Alzheimer’s in Humans, Path To A Cure?
An animal model using adult rhesus monkeys mimics some of the earliest abnormalities of Alzheimer’s disease. This could give us a better understanding of how the disease begins in humans and pave the path to a cure of this devastating disease.
Developed by scientists at the California National Primate Research Center of the University of California, Davis, this preliminary model provides some hope that it can translate well to human clinical studies.
To this point, most animal models investigating early-onset Alzheimer’s are based on single-gene mutations. In the current study, researchers instead created a model that studies how protein fragments affect an area of the brain, called the prefrontal cortex. Indeed, previous studies demonstrated that the pre-frontal cortex functions in the same way for both adult rhesus monkeys and humans.
Animal Model: A Novel Approach
The researchers focused on impairment to synapses, the tiny connections between neurons through which electrical or chemical signals pass. Neurons communicate with each other and transmit instructions and information. Examples are short and long term memory as well as information processing.
Keeping these neurons and synapses in good working order could be the key to preventing neuronal death, inflammation and other Alzheimer’s-related brain damage. Such damage can lead to age-related cognitive decline and dementia.
To create the model, the researchers injected four female monkeys with soluble forms of amyloid-beta protein fragments, called oligomers. These oligomer fragments accumulate in the Alzheimer’s brain and trigger synapse failure. Two monkeys received a control peptide, and three others received no injections.
Cerebrospinal fluid was collected to analyze Alzheimer’s biomarkers. The researchers looked for changes in the dorsolateral prefrontal cortex (DLPC). This area of the brain controls cognitive functions such as working memory, planning, and abstract reasoning. All of these functions deteriorate in people with Alzheimer’s.
Animal Model: Study Results
The DLPC monkeys that received the oligomers accumulated a type of neuron that is vulnerable to damage caused by Alzheimer’s in humans. A computerized, 3D reconstruction of their brain showed that the oligomers reduced the ability of neurons to communicate with each other.
In addition, the monkeys exposed to the oligomers had a greater number of microglial cells. These cells cause brain damage characteristic of early Alzheimer’s disease, when activated by disease or aging.
Also, their cerebrospinal fluid also showed very early stages of Alzheimer’s pathology in humans.
The study shows that rhesus monkeys may be a good model for studying the early neuronal dysfunction of Alzheimer’s disease.
Future research will focus on developing drugs that can prevent this breakdown in cell communication.
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