Biomarkers

Area of Science:

• Neurology
• Biomarker Research
• Gerontology

Background:

• Research on Alzheimer's disease and related dementias (ADRDs) biomarkers has largely focused on amyloid-beta and tau pathologies.
• Studies investigating biomarkers of glial and neuronal dysfunction and neuroinflammation in community cohorts are limited.
• This study examines novel blood biomarkers associated with cognitive decline and dementia risk.

Purpose of the Study:

• To investigate the association of blood biomarkers reflecting glial/neuronal dysfunction and neuroinflammation with cognitive decline over 25 years.
• To assess the relationship between these biomarkers and the risk of developing dementia.
• To explore the utility of these biomarkers in early ADRD diagnosis and risk stratification.

Main Methods:

• 1,864 participants from the ARIC study had blood biomarkers (sCD14, YKL-40, GFAP, NfL, total-Tau, UCH-L1) measured.
• Cognitive function was assessed up to six times over 25 years, and dementia cases were identified through various ascertainment methods.
• Shared parameter models were used to analyze cognitive decline and dementia risk associated with each biomarker, adjusting for covariates.

Main Results:

• Higher levels of most biomarkers (all but UCH-L1) were associated with faster cognitive decline and increased dementia risk.
• For instance, a one SD increase in YKL-40 was linked to steeper cognitive decline and a 59% higher dementia hazard.
• sCD14 was also associated with accelerated cognitive decline and a 38% increased dementia hazard.

Conclusions:

• Blood biomarkers indicating microglial activation, astrocytic reactivity, and neuronal degeneration are associated with cognitive decline and dementia risk.
• These findings suggest potential utility for these biomarkers in ADRD risk stratification and intervention strategies.
• Further research will explore differences in these associations based on race and APOE-ε4 status.