[Reading Science] Dementia in Old Age Depends on Protein Balance in Middle Age

Research by US National Institute on Aging
Identifies 32 Dementia-Related Proteins
Regulate Protein Degradation and Immune System
Deficiency or Excess Causes Dementia

Dementia is the greatest threat to elderly health in the aging era. About one in ten people over the age of 65 suffer from it. It is so fatal that it is nicknamed 'the cruelest farewell' due to memory loss and behavioral disorders. However, a study has revealed that the occurrence of dementia in old age is deeply related to the balance of proteins in the body during middle age. This supports doctors' advice that "drinking just one glass of milk a day can help prevent dementia."

A research team from the U.S. National Institute on Aging published a paper containing these findings on the 19th in the international journal Science Translational Medicine. The team recruited over 10,000 participants starting in 1987 and conducted a long-term follow-up study. Participants underwent six examinations over 30 years, and about 20% developed dementia. The researchers regularly collected blood samples from participants to examine the proteome (all proteins produced within the human body) and studied whether changes in specific protein levels could serve as predictors of dementia. They checked for dysregulation?whether individual protein levels in the blood were significantly higher or lower than normal?over approximately 25 years.

As a result, the team identified 32 proteins whose deficiency or excess in the blood at middle age (45 to 60 years old) appeared strongly associated with the development of dementia in old age. Although the exact mechanisms have not yet been clarified, the researchers asserted, "The likelihood that this connection is merely coincidental is very low."

In particular, the team confirmed that proteins related to the protein degradation process (proteostasis) are associated with dementia. The human body breaks down excess specific proteins in the blood to prevent them from deteriorating and clumping. Problems in this process can cause dementia. The most common Alzheimer's dementia occurs when tau proteins, amyloid proteins, and others accumulate excessively within brain nerve cells without being broken down for unknown reasons, impairing their function. The researchers observed changes in the levels of proteins related to this degradation process in the brain cells of people who died from Alzheimer's dementia and in the blood of living patients. The international journal Nature explained that "these protein degradation-related proteins are associated with the presence of amyloid and tau proteins and suggest a certain involvement in the onset of dementia."

Kennan Walker, a researcher at the U.S. National Institute on Aging, said, "A single person's proteome alone does not predict the risk of developing dementia," but added, "When combined with existing variables such as age and family history, the prediction of onset likelihood can be made more accurate."

Among the 32 dementia-related proteins, some were not associated with changes in plasma or brain tissue. A representative example is a protein called GDF15, which is not detected in the brain at all. The research team suggested that this indicates dementia is not simply a brain-only problem but that various parts of the body below the neck connected to the brain also play certain roles. Additionally, they confirmed changes in the levels of proteins related to the body's immune system. This provides further evidence supporting the hypothesis that innate and adaptive immune functions play certain roles in the onset of dementia.

Nicholas Saifrid, a professor at Emory University, said, "More research is needed to understand exactly what physiological roles these proteins play in the onset and progression of dementia," and evaluated, "To benefit actual patients, a clearer and more detailed understanding of the fundamental mechanisms is necessary. If successful, this could become an opportunity to establish early dementia treatments and preventive methods."