Background: Blood biomarkers are an essential tool for diagnosing and monitoring AD/ADRD progression. In this study, we have evaluated their relationship with amyloid and tau PET imaging.
Methods: 191 participants were enrolled at the NYU Alzheimer's Disease Research Center (ADRC). PET scans were conducted on patients to assess cerebral tau and amyloid burden. Subjects were categorized into three groups: cognitively unimpaired (CU) (n = 66; mean age= 71.6, 59% female), subjective cognitive decline (SCD) (n = 100; mean age= 75.5, 73% female), and mild cognitive impairment (MCI) (n = 25; mean age= 73.6, 68% female). Amyloid PET imaging was conducted in 186 subjects; tau PET imaging was conducted in 144 subjects. Plasma assays measured Aβ40, Aβ42, NfL, GFAP, and pTau181 levels using SIMOA HD-X. Neuroinflammation and BBB dysfunction were quantified using SIMOA SP-X.
Results: Linear regression was conducted to assess the relationship between amyloid PET SUVR and plasma biomarkers after adjusting for age, sex, APOE ε4 status, and cognitive group. Higher amyloid PET SUVR was associated with older age (p = 0.005) and APOE ε4 status (p < 0.001). Compared with MCI, both CU and SCD participants had significantly lower amyloid PET SUVR (CU: standardized β = -0.82, 95% CI [-1.26, -0.38], p<0.001; SCD standardized β= -0.61, 95% CI [-1.03, -0.19], p = 0.005). Higher amyloid PET SUVR was significantly associated with higher pTau181 (standardized β = 0.26, 95% CI [0.10, 0.42], p = 0.001), and pTau181/Aβ42 ratio (standardized β = 0.28, 95% CI [0.13, 0.43], p < 0.001). Higher tau PET SUVR was significantly associated with a lower plasma Aβ42 (standardized β = -0.21, 95% CI [-0.40, -0.04], p = 0.020), older age (standardized β = 0.26, 95% CI [0.08, 0.43], p = 0.005), higher GFAP (standardized β = 0.23, 95% CI [0.04, 0.42], p = 0.020), and lower hIL8 levels (standardized β = -0.28, 95% CI [-0.45, -0.12], p < 0.001).
Conclusion: Amyloid and tau PET SUVR increases were associated with changes in plasma biomarker levels, making a strong case for their use as non-invasive markers to correlate with pathology development in patients at pre-dementia stages.