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Scientists have identified new proteins linked to the risk of developing dementia 25 years later. Lucas Ottone/Stocksy
  • Dementia is not an inevitable consequence of aging, but increasing numbers of people are affected by it, with Alzheimer’s disease being the most common form.
  • Early diagnosis and intervention benefit people with dementia and their carers, so the search is on for early markers of the disease.
  • Now, a long-term study in middle-aged people has identified 32 proteins that are linked to later development of Alzheimer’s.
  • The researchers suggest that these proteins should be further studied as possible predictors of Alzheimer’s.

According to the Alzheimer’s Association, more than 6 million Americans are living with Alzheimer’s disease, the most common form of dementia. The World Health Organization estimates that 70% of the 55 million dementia cases worldwide are due to Alzheimer’s.

Treatments can help relieve symptoms of Alzheimer’s but there is, as yet, no cure for the disease. However, new medications are showing promise in trials.

In trials, new monoclonal antibody treatments — donanemab, lecanemab, and aducanumab, which clear amyloid proteins from the brain — appear to slow disease symptoms’ development.

Trials have shown that these medications are most effective if given when the disease is in its first stages, so early diagnosis is vital to treatment. Trial results just released for donanemab suggest that if given soon after symptoms appear, the drug significantly slows the clinical progression of Alzheimer’s.

A new study of people ages 45–65 has identified proteins that are linked to later development of Alzheimer’s.

The study is published in Science Translational Medicine.

The researchers call for further research into these proteins, which could indicate an increased risk of Alzheimer’s and aid early diagnosis.

In this study, the researchers were hoping to identify proteins that are abnormally expressed in middle-aged adults (defined as those ages 45–65) who develop dementia later in life.

At the start of the study, in 1993–1995, researchers took blood samples from 10,981 participants with a mean age of 60. They then analyzed more than 4,800 plasma proteins from these blood samples.

During the 25-year follow-up period, 1,874 (17%) of the participants were diagnosed with dementia.

The researchers identified 32 plasma proteins that were associated with dementia risk. The strongest association was for GDF15, a protein involved in metabolic and immunoregulatory function, inflammation, and oxidative stress.

They then investigated which of the proteins were associated with near-term (within 15 years of protein measurement) and long-term (more than 15 years from protein measurement) dementia risk.

Seven midlife proteins were associated with near-term dementia risk, among them GDF15, and proteins involved in the functioning of nerves and synapses, immunity, growth factor binding, and breakdown of proteins.

GDF15 was also associated with long-term dementia risk, together with six other proteins that were not highlighted at the 15-year point, suggesting that the biological pathways associated with dementia risk change over time.

Some of the proteins were also found in brain tissue. However, the researchers did not detect GDF15, which was associated with dementia risk, both near-term and long-term, in brain tissue.

They suggest that it is not an Alzheimer’s-specific protein, but is linked to neuroinflammation, which is associated with age-related disease.

The researchers did not find any direct causal relationships between proteins and Alzheimer’s, but they believe that they have “identified a number of pathway-specific plasma proteins that may be relevant in the earliest phase of Alzheimer’s and related dementias.”

“Although the dementia-associated proteins alone did not provide a highly accurate prediction of 25-year dementia risk, these proteins, in combination, did add modest predictive value to a group of demographic and clinical variables which are themselves strong predictors of dementia risk.”
— Study authors

The researchers suggest that the proteins they have identified should be the basis for further research, as they may be predictive markers for dementia.

They also suggest that their findings may provide insight into relevant biological pathways and facilitate the identification of early-stage markers and molecular drivers of disease.

So, with further research, these proteins may be useful in assessing a person’s risk of developing dementia. Whether they may help lead to new diagnostic tests for dementia remains to be seen.