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In a study new proteins associated with the risk of dementia were identified. 25 years have gone by.

Is it possible to foresee the risk of dementia decades in advance? In a study published in Science Translational Medicine on Wednesday, neuroscientists reported a startling discovery.

Neuroscientists from the National Institute on Aging and the Johns Hopkins University School of Medicine examined over 4,000 proteins found in plasma, which is blood without red blood cells. Nearly 11,000 adults aged 45 to 65 were analyzed to determine the relationship between the proteins and the risk of dementia.

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After 25 years, they discovered that 32 proteins may be essential to the early onset of dementia, suggesting that they could be used to predict the disease in younger people.

Nicholas Seyfried, a biochemistry and neurology professor at the Emory University School of Medicine, remarked, “The study is robust and impressive.” It is genuinely remarkable. Seyfried, who was not involved in the study, stated that it sheds light on one of the most essential questions facing Alzheimer’s research, a historically complex and difficult field.

Alzheimer’s disease is an incapacitating brain disorder that robs victims of their memories and cognitive abilities. It is the most common cause of dementia, also known as memory loss, in people aged 65 and up.

Alzheimer’s disease is responsible for up to 80% of dementia cases in the United States, where it impacts nearly 7 million individuals. Despite scientific advancements, including the development of therapies, the early brain changes underlying dementia remain poorly understood.

The ability to predict dementia years prior to cognitive decline could offer promise for early intervention in Alzheimer’s disease. “Imagine telling a 45- or 50-year-old individual that their plasma biomarker profile suggests they will develop dementia within the next 10 to 15 years,” Seyfried told STAT. “That would be a profound statement.

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The identified proteins, according to Keenan Walker, co-leader of the study, can assist researchers in understanding the alterations that lead to dementia. They could then be used as biomarkers to predict whether a person will develop the disease decades before cognitive decline.

Walker and his colleagues will need to conduct additional research before the proteins can be validated and used as predictive markers in routine clinical tests for dementia. However, the findings highlight a growing interest in identifying the early biological signatures of Alzheimer’s disease, which are brain changes that occur before the onset of symptoms.

There are already two proteins, amyloid beta, and tau, that alter brain cells abnormally and help neurologists identify Alzheimer’s disease symptoms. Although research demonstrates that amyloid and tau, like the spark that ignites a forest fire and the fuel, cause healthy neurons to degenerate into a diseased state, many of the changes that occur over time in the brain and contribute to dementia remain obscure.

32 of the more than 4,000 proteins that Walker and his colleagues analyzed were associated with dementia in their study. “We were able to determine, one by one, which proteins predicted new-onset dementia,” said Walker, a National Institute on Aging researcher who investigates age-related cognitive disorders.

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In addition, the study revealed that the proteins were involved in alterations to essential cellular functions, including immunity, synaptic function, proteostasis, and extracellular organization. Walker stated that this indicates a possible onset of dementia in high-risk individuals decades prior to the outset of Alzheimer’s disease symptoms such as neurodegeneration and loss of brain function. “Alzheimer’s disease biology is really expressed early on,” he said.

The team investigated whether the proteins were associated with neurocognitive outcomes that are clinically recognized. Twelve of the 32 proteins associated with dementia were linked to biomarkers for Alzheimer’s disease in cerebrospinal fluid, a window into the brain. “The relationship between these proteins and the known biomarkers for Alzheimer’s disease, as well as the incorporation of brain changes, significantly strengthens the conclusions,” said Seyfried.

Eight of these candidate protein markers were expressed abnormally in the postmortem brain tissue of Alzheimer’s patients. However, some of the most significantly associated signature proteins with dementia risk, such as GDF15, were not detected in brain tissues. This, according to Seyfried, may indicate molecular alterations in the peripheral nervous system below the neck that influence the risk of developing dementia.

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Instead of using sophisticated brain imaging techniques to detect the known proteins amyloid and tau, researchers could use protein biomarkers in blood plasma to predict the risk of developing dementia.

While the study is persuasive, it does have some limitations. The researchers only recruited Black and White participants from communities throughout the United States. Thus, the results may not be representative of populations that are not Black or White. Seyfried concurs that this is a problem and that there is a need for additional research in a population with such vast ethnic diversity.

Seyfried stated, “The validity of the study cannot be questioned.” However, we must determine if these identifiers apply to the entire population.

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