Association of plasma abeta and tau levels in relation to cognition and brain structure in a diverse community: Biomarkers (non‐neuroimaging): Method development and validation. (7th December 2020) - DeCarli, Charles
Abstract: Background: Early studies of mostly non‐Hispanic White groups suggest that plasma tau and abeta levels are associated with clinically relevant cognitive impairment. Given limited studies of more ethnically diverse communities, we chose to study 402 subjects from the UC Davis Alzheimer's Disease Center. Method: The subjects were diverse (14% White, 45% Black and 41% Hispanic), 61% women, average age of 76 + 7.3 years with 12 + 5 years of education with a spectrum of cognitive ability (66% cognitively normal, 19% MCI and 15% demented). Plasma samples were obtained within 0.3 + 0.8 years of cognitive and MRI assessments. Duplicate plasma samples were measured for tau, abeta 40 and 42 on a Quanterix SRX using SIMOA technology. Subjects with CV >20% or extreme values (>5 SD) were excluded. Analyses compared cross‐sectional associations between plasma abeta and tau levels and diagnosis adjusting for age, sex, race/ethnicity and education as well as associations with memory, executive function and structural MRI measures. Result: The table summarizes mean values for Tau, abeta 40, 42 and the 42/40 ratio across diagnoses and race/ethnicity. Both abeta 42 and the 42/40 ratio differed significantly by clinical diagnosis. The abeta 42/40 ratio was significantly lower for non‐Hispanic whites than Blacks and Hispanics (Tukey HSD, p <0.05). Higher plasma tau levels were weakly negatively associated (beta =‐0.04 + 0.02, <0.05) whereas higher abeta 42/40 ratios were significantly positively associated (beta = 6.6 + 2.9, p =0.02) with executive function. Higher abeta 42/40 ratios were also significantly positively associated (beta = 7.1 + 3.4, p <0.05) with hippocampal and temporal lobe gray matter (beta = 146 + 46, p =0.002) volumes. Logistic regression predicting diagnostic category found that the abeta 42/40 ratio significantly differentiated the groups (chi sqr =17, p = 0.0002). Conclusion: In this study of diverse, community recruited individuals, plasma abeta 42 and the abeta 42/40 ratio were significant predictors of clinical diagnosis, cognition and MRI measures, indication that plasma levels of abeta measured have clinical implications in a diverse cohort where mixed pathologies are known to be common 1 . Reference: 1.Filshtein TJ, Dugger BN, Jin LW, et al. J Alzheimers Dis 2019.