The higher the amount of this protein you have in your brain, “the more likely you are to be cognitively intact.”
In the same way that a telephone cord links the handset to the receiver, neurons must establish physical connections with one another to facilitate communication and signal transmission, thus enabling cognitive functions such as thinking and speaking.
A recent study published in Molecular & Cellular Proteomics presents evidence that a protein known as neuritin may help certain individuals maintain their neuronal connections even in the presence of toxic substances associated with Alzheimer’s disease, which typically work to dismantle these vital links.
Alzheimer’s disease is the leading cause of dementia, impacting over 5.8 million individuals in the United States. To identify this condition, doctors employ a combination of cognitive assessments, physical and neurological examinations, brain imaging techniques, spinal fluid tests, and a review of the patient’s medical history. The majority of affected individuals exhibit cognitive deterioration along with the presence of harmful proteins in their brains, resulting in the destruction of neurons and a reduction in brain size.
These detrimental protein accumulations, known as amyloid-beta plaques and tau tangles, can interfere with neuronal connections and communication. This disruption is what causes the memory impairment and disorientation that are typically associated with Alzheimer’s disease.
Interestingly, some people exhibit the telltale signs of Alzheimer’s pathology in their brains upon examination but do not experience cognitive decline. Researchers have labeled these individuals as “cognitively resilient” in the new study.
But why?
Scientists Jeremy Herskowitz (an associate professor of neurology at the University of Alabama at Birmingham) and Nicholas Seyfried (a professor of biochemistry at the Emory University School of Medicine and the project’s co-supervisor) pooled their expertise in proteomics and basic neurology to answer this question.
Unlike most research, which is based on hypotheses, this team first looks at sick people and their cells to find possible treatments.
“Our research collectively identifies differences in humans first. Then, after that discovery is made, we can ask questions in experimental model systems to work out what’s going on at the molecular and cellular level,” Herskowitz added.
They performed an extensive mass spectrometry analysis on proteins present in the brains of individuals with normal cognitive function, those with Alzheimer’s disease, and those demonstrating cognitive resilience. Cheyenne Hurst, an Emory University graduate student and co-principal investigator of the research, employed advanced computational methods to establish a connection between neuritin levels and the preservation of cognitive abilities over time.
“The higher the amount of neuritin you have in your brain, the more likely you are to be cognitively intact,” Hurst commented.
The next step was for the researchers to examine how the protein affected neural communication. In order to do this, scientists extracted neurons from the rat hippocampus and subjected them to neuritin, pathogenic amyloid beta, or both.
Co-lead author and UAB graduate student Derian Pugh saw differences in the way the three groups were put together.
“The dendritic spines or synapses coming off healthy neurons kind of remind me of branches on a tree,” Pugh added.
However, the connections between the neurons in the pathogenic amyloid beta-exposed neurons as well as their structural integrity were all compromised. They “looked like a tree with branches,” according to Pugh.
Neuritin, however, fully obstructed amyloid beta’s negative effects on the neuron cultures.
“With these experiments, we were able to recapitulate what happens in humans that display cognitive resilience and a possible mechanism,” Herskowitz added.
The team wants to concentrate on neuritin’s fundamental biology as well as how to use it as a diagnostic or treatment tool for Alzheimer’s disease.
“The ability to estimate the amount of amyloid beta pathology in an older person’s brain using biomarkers is getting very advanced,” Seyfried added.
“We can predict quite accurately the presence of amyloid beta is in someone’s brain while they’re still alive.
“If they have a large amount of amyloid beta, but they’re still cognitively normal, they may want to one day get treated with neuritin or drugs that boost neuritin levels so that those symptoms don’t develop into dementia.”
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