Biomarkers

Alzheimer's disease (AD) specific biomarkers, including blood p-Tau, tau PET, and amyloid PET, are excellent predictors of AD pathology. However, the potential of these biomarkers-along with neuroinflammation markers such as GFAP and NfL-to predict short-term cognitive and functional decline in patients with mild cognitive impairment (MCI) and mild dementia has not been extensively explored.

Participants with memory-predominant MCI and mild dementia were recruited from a tertiary care memory clinic in Bangkok, Thailand. At baseline, Tau PET (PI-2620) and amyloid PET (Florbetaben) were performed, blood samples were collected to measure plasma p-Tau-181, p-Tau-217, GFAP, and NfL. Cognitive and functional abilities were assessed using the Thai version of the MoCA and CDR-SB scales at baseline and a 24-month follow-up. "Progressors" were defined as participants who experienced a decline in MoCA scores by >3 points or an increase in CDR-SB scores by >1 point. We employed Wilcoxon rank-sum tests to compare biomarker levels between progressors and non-progressors, and biomarker performance was assessed via ROC analysis.

Among 42 participants (median age: 71 years, 66.7% female), 26 (61.9%) were classified as progressors. Median (IQR) amyloid PET centiloid levels (56.7 [33.0-102.0] vs. 16.1 [5.3-61.3], p = 0.026) and Tau PET SUVR for Braak stages 3-4 (1.5 [1.2-2.1] vs. 1.1 [1.0-1.2], p <0.001) were significantly higher in progressors. Plasma p-Tau-217 (11.1 [7.1-21.0] vs. 4.0 [2.4-9.6] pg/mL, p = 0.004) and GFAP levels (206.7 [140.6-322.0] vs. 114.5 pg/mL [92.6-192.7], p = 0.003) were also significantly higher in progressors, while plasma p-Tau-181 and NfL levels showed no significant differences between groups (Figure 1). Tau PET SUVR provided the best prognostic value for 24-month progression (AUC 0.84, 95% CI 0.71-0.96), followed by plasma GFAP (AUC 0.78, 95% CI 0.62-0.94) and plasma p-Tau-217 (AUC 0.77, 95% CI 0.61-0.92) (Figure 2).

Tau PET SUVR in Braak stages 3-4 is a robust marker for short-term cognitive and/or functional deterioration. Plasma p-Tau-217 not only serves a diagnosis but also has prognostic capabilities. Plasma GFAP outperforms plasma NfL in predicting short-term progression. Future studies should focus on the value of these biomarkers in long-term progression.