Protein Levels in Plasma Highly Predictive of Future Dementia Risk According to UK Biobank Study

People with higher baseline plasma levels of certain proteins, including glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), growth/differentiation factor 15 (GDF15), and latent-transforming growth factor beta-binding protein 2 (LTBP2), had an elevated risk of developing dementia, particularly Alzheimer disease (AD) and vascular dementia (VaD). GFAP and LTBP2, in particular, were found to be highly specific for predicting dementia, and individuals with higher GFAP levels were more than twice as likely to develop dementia. These findings are based on data published in Nature Aging related to a comprehensive prospective cohort study of the UK Biobank.

The study included 52,645 adult participants without dementia at baseline from the UK Biobank recruited from 22 assessment centers in the United Kingdom. Blood samples were collected between 2007 and 2010, which were analyzed using Olink Explore Proximity Extension Assay to measure proteomic data for 1463 unique proteins associated with inflammation, cardiometabolic health, neurology, and oncology. There were 1417 (2.7%) incident cases of dementia identified within the study population during a median follow up of 14.1 years, with 691 participants diagnosed with AD and 285 diagnosed with VaD.

Analysis of study results revealed that:

• Higher NfL levels (hazard ratio [HR], 2.36), GFAP levels (HR, 2.32), and GDF15 levels (HR, 1.70) at baseline were associated with elevated risk of developing dementia.
• Higher levels of GFAP at baseline were found to increase an individual’s risk of developing AD by a factor of 2.91.
• Higher GDF15 levels at baseline were associated with a 2.45 times greater likelihood for an individual to develop VaD.
• Additionally, individuals who had higher baseline levels of LTBP2 were at a greater risk of developing all-cause dementia (ACD) or AD, and LTBP2 was found to be highly specific as a predictor for dementia diseases.