Biomarkers.

Area of Science:

• Neuroscience
• Biomarker Discovery
• Alzheimer's Disease Research

Background:

• Alzheimer's disease (AD) is a complex neurodegenerative disorder with a long preclinical phase.
• Monitoring pathological changes like neurodegeneration and inflammation may enable early intervention.
• Multi-biomarker assessment can guide personalized therapeutic strategies.

Purpose of the Study:

• To identify cerebrospinal fluid (CSF) biomarkers for predicting dementia progression.
• To explore biomarkers associated with neurodegeneration, inflammation, and metabolic stress in cognitive decline.
• To assess the utility of biomarkers in differentiating individuals at risk of progressing to dementia.

Main Methods:

• Measured 54 CSF biomarkers in individuals with AD dementia, MCI progressors, MCI non-progressors, and SCD using MULTI-ARRAY technology.
• Selected biomarkers targeting neurovascular dysfunction, inflammation, neurodegeneration, tissue injury, and metabolic stress.
• Utilized ANOVA and ROC curve analysis (AUC) to determine group differences and predictive utility.

Main Results:

• 30 CSF biomarkers showed significant concentration differences across cognitive groups.
• 17 analytes differed significantly between MCI progressors and non-progressors.
• Ten proteins, notably pTau217 (AUC > 0.99), demonstrated high accuracy in predicting MCI progression to dementia.

Conclusions:

• Identified novel CSF biomarkers indicative of dementia or progression to dementia, reflecting diverse pathological mechanisms.
• These biomarkers show potential for personalized treatment and stratification in clinical trials.
• Further integration into panels may enhance understanding of early AD pathology and progression.