Fight Aging!

The search for ways to determine whether someone is in the very early stages of developing dementia overlaps with the development of means to determine biological age. The first step in both cases is to gather a sizable database of omics data, usually from blood samples. Once that data is in hand, why not try to achieve both goals? Alzheimer's disease and other neurodegenerative conditions may exhibit years to decades of slow development prior to evident symptoms, and those underlying processes will show up given the right measurements. The research noted here is one example of the exploration of biomarkers that is presently taking place, in search of ways to predict the onset of neurodegeneration.

A study that followed thousands of people over 25 years has identified proteins linked to the development of dementia if their levels are unbalanced during middle age. Most of the proteins have functions unrelated to the brain. "We're seeing so much involvement of the peripheral biology decades before the typical onset of dementia." Equipped with blood samples from more than 10,000 participants, researchers questioned whether they could find predictors of dementia years before its onset by looking at a person's proteome - the collection of all the proteins expressed throughout the body. They searched for any signs of dysregulation - when proteins are at levels much higher or lower than normal. The samples were collected as part of an ongoing study that began in 1987. Participants returned for examination six times over three decades, and during this time, around 1 in 5 of them developed dementia.

The researchers found 32 proteins that, if dysregulated in people aged 45 to 60, were strongly associated with an elevated chance of developing dementia in later life. It is unclear how exactly these proteins might be involved in the disease. For example, one of the proteins found with the strongest association with dementia risk - called GDF15 - was not detected in the brain. The study found altered levels of many of the proteins both in the brain tissues of those who had died with Alzheimer's disease, and in the blood of those still living with it. These were associated with the presence of amyloid and tau proteins, which suggests they are somehow involved in processes specific to the disease. Other proteins identified in the study were linked to the immune system, adding to growing evidence for the role of innate and adaptive immune function in dementia.

Link: https://doi.org/10.1038/d41586-023-02374-2