Plasma P‐tau181 levels predict amyloid pathology in cognitively unimpaired individuals after 10 years

Abstract

AbstractBackgroundPlasma levels of phosphorylated‐tau (P‐tau) are able to identify core Alzheimer’s Disease (AD) pathologies, but its value in cognitively unimpaired individuals needs further study. We aimed to investigate the value of plasma P‐tau at threonine‐181 (P‐tau181) for predicting amyloid pathology in cognitively unimpaired individuals followed over 10 years.MethodFrom the EMIF‐AD PreclinAD study we selected 74 individuals, aged 60 years and older (Table 1) with normal cognition, that had plasma samples available that were collected at time of amyloid status assessment, as well as 10 years earlier (median (IQR) = ‐9.7 (2)). Amyloid status was defined using visual read of dynamic [18F]flutemetamol‐PET images or CSF amyloid‐β1‐42/1‐40<0.065 (Euroimmun). Simoa assays were applied to measure plasma P‐tau181 levels (Eli Lilly). ROC curve analysis was used to determine the value of plasma P‐tau181 in predicting amyloid status. Further, linear mixed models, adjusted for age and sex, were applied to assess longitudinal change in plasma P‐tau181, using time and the interaction between time and amyloid status as a predictor.ResultAmyloid‐positive individuals had higher plasma P‐tau181 levels compared to amyloid‐negative individuals, both at time of amyloid status assessment and 10 years earlier. Plasma P‐tau181 obtained 10 years prior to amyloid status assessment was able to discriminate amyloid status with similar high Area Under Curve, sensitivity and specificity as plasma P‐tau181 obtained at time of amyloid status assessment (Figure 1). Longitudinally, we observed a general increase in plasma P‐tau181 levels over time (β=0.10, p<.001). Interestingly, amyloid‐positive individuals showed a steeper increase in plasma P‐tau181 levels over 10 years compared to amyloid‐negative individuals (time*amyloid‐β‐interaction: β=0.16, p=.005 (Figure 2)).ConclusionOur data suggest that plasma P‐tau181 can be used to predict AD pathology in cognitively unimpaired individuals. The high discriminative value observed, even using plasma P‐tau181 collected 10 years prior to amyloid status assessment, indicates the potential of this marker as an early amyloid pathology pre‐screening tool in the normal aging population. The observed amyloid dependent longitudinal increases in plasma P‐tau181 levels indicates this marker to be eligible for disease monitoring.