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Dementia Prediction Biomarkers Pinpointed in Plasma Proteomics Study

NEW YORK – A team led by investigators at Fudan University has unearthed proteomic biomarkers in plasma samples from healthy adults that appear to coincide with their risk of developing dementia in the future.

"Our findings strongly highlight GFAP as an optimal biomarker for dementia prediction, even more than 10 years before the diagnosis," the authors wrote in a paper published in Nature Aging on Monday, adding that the results "are poised to yield significant implications for screening people at high risk for dementia and for early intervention."

With Olink assay-based profiles of 1,463 plasma proteins for 52,645 UK Biobank participants with available electronic health record data, the researchers used a proteome-wide association study approach to search for proteins coinciding with neurodegenerative conditions ranging from all-cause dementia (ACD) or vascular dementia (VaD) to Alzheimer's disease (AD) later in life. The participants included 1,417 individuals who developed dementia within a median follow-up time of 14.1 years after their blood samples were taken.

"Although some blood markers have been proven to be strongly associated with dementia risk, biomarker discovery efforts have typically focused on one or a small number of proteins because of technical constraints, and lacked the systemic comparison of human proteomics," the authors wrote, noting that the current study "innovatively identified important plasma biomarkers for future dementia prediction from the largest prospective community-based cohort with long-term follow-up to date."

The association analyses pointed to hundreds of potentially predictive plasma proteins, including 184 linked to ACD, 139 VaD-associated proteins, and 16 proteins associated with AD, though the associations did not reach statistical significance.

After taking vascular variables into account, the team tracked down four plasma proteins with significant ties to ACD, VaD, or AD risk: GFAP, NEFL, GDF15, and LTBP2.

Those four proteins "consistently had the most significant associations with future dementia events and showed high importance in prediction tasks in 5-year, 10-year, over 10-year, and all-time scenarios," co-senior author Jin-Tai Yu and co-first author Yu Guo, researchers at Fudan University, said in an email.

While levels of the GFAP and NEFL proteins appeared to start rising in the blood at least 10 years before individuals were diagnosed with dementia, the GFAP and LTBP2 proteins appeared to have the highest specificity when it came to predicting dementia, they explained, prompting them to take a closer look at the predictive performance of GFAP.

Indeed, models that combined plasma GFAP measurements with demographic data led to improved ACD, VaD, and AD prediction stretching out a decade, the team reported, noting that higher-than-usual blood plasma levels of GFAP were linked to a 2.32-fold increase in dementia risk.

Together, Yu and Guo noted, findings from the study pointed to "important plasma biomarkers for the prediction of future dementia, which provides a new theoretical basis for the transition of blood testing from scientific research to clinical application," calling the results "of great significance for the screening and early intervention" in those at high risk of developing dementia.