Breakthrough Study: Four Proteins Could Predict Dementia 10 Years in Advance

Researchers have discovered four plasma proteins that can be used to predict the risk of developing all-cause dementia (ACD), Alzheimer’s disease (AD), and vascular dementia (VaD) ten years before diagnosis.

A team led by Dr. Weijing Cai from Fudan University in Shanghai, China, analyzed the relationship between plasma proteins and the onset of dementia in over 52,000 adults registered in the UK Biobank. They identified four proteins that can be used as long-term dementia risk predictors, as reported in the scientific journal Nature Aging on the 13th.

Previous studies have investigated plasma proteins as biomarkers for long-term dementia risk prediction in healthy adults. Still, most have focused on one or a few proteins or lacked large-scale data, such as from the UK Biobank.

The research team also pointed out that previous studies neglected how these proteins could predict the onset of all-cause dementia, Alzheimer’s disease, and vascular dementia over a prolonged period of up to 10 years.

The team examined plasma biomarkers related to dementia prediction in data from 52,645 dementia-free participants (median age 58) registered in the UK Biobank. It investigated how each biomarker predicted the onset of ACD, AD, and VaD over a median period of 14.1 years.

During the follow-up observation period, a total of 1,417 people were diagnosed with dementia. Among them, 833 people were diagnosed with dementia within the first ten years of the study, including 219 who developed dementia within five years and 584 people who developed dementia after ten years.

The research team discovered that four out of the 1,463 plasma proteins included in the analysis were consistently associated with the onset of all-cause dementia, Alzheimer’s disease, and vascular dementia.

The four plasma proteins are Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light Polypeptide (NEFL), Growth Differentiation Factor 15 (GDF15), and Latent Transforming Growth Factor Beta Binding Protein 2 (LTBP2).

The team developed a 10-year prediction model for ACD, AD, and VaD based on these findings. All four proteins showed high predictive power, with GFAP, which has long been noted as a dementia-related factor, showing the strongest association with dementia.

People with high GFAP levels were 2.32 times more likely to develop dementia than those with lower levels. In particular, GFAP and LTBP2 showed very high specificity in predicting dementia, and GFAP and NEFL began to show changes at least ten years before a dementia diagnosis.

The research team said that this shows the potential for GFAP to be a latent biomarker for evaluating the risk of all-cause dementia, Alzheimer’s disease, and vascular dementia in the early stages. They added that these findings provide significant implications for identifying high-risk dementia groups and earlier interventions.