Plasma biomarkers predict longitudinal amyloid accumulation, tau burden, brain atrophy and cognitive decline in early Alzheimer’s disease

Abstract

AbstractBackgroundIt is currently unclear whether plasma biomarkers can be used as independent prognostic tools for early Alzheimer’s disease (AD). In this study we sought to address this question by assessing whether plasma biomarkers can predict changes in amyloid load, tau accumulation, brain atrophy and cognition in non‐demented individuals.MethodTo achieve this, plasma amyloid‐β 42/40 (Aβ42/40), phosphorylated‐tau181 (P‐tau181), phosphorylated‐tau217 (P‐tau217) and neurofilament light (NfL) were determined in 120 non‐demented individuals, 123 patients with AD dementia and 15 patients with a non‐AD dementia from the Swedish BioFINDER‐2 study, who underwent longitudinal amyloid (18F‐flutemetamol) and tau (18F‐RO948) positron emission tomography (PET), structural magnetic resonance imaging (T1‐weighted) and cognitive testing.ResultOur univariate linear mixed effect models showed there were several significant associations between the plasma biomarkers with imaging and cognitive measures. However, when all biomarkers were included in the same multivariate linear mixed effect models, we found that increased longitudinal amyloid‐PET signals were independently predicted by low baseline plasma Aβ42/40 (p = 0.011), whereas increased tau‐PET signals, brain atrophy and worse cognition were independently predicted by high plasma P‐tau217 (p < 0.004). These biomarkers performed equally well or better than the corresponding biomarkers measured in the cerebrospinal fluid and showed a similar performance to binary plasma biomarker values, which can be more easily implemented in the clinic and were defined using the Youden index as the optimal cut‐offs that could discriminate a sample of Aβ‐negative cognitively normal individuals from AD dementia patients. In addition, plasma Aβ42/40 and P‐tau217 did not predict longitudinal changes in patients with a non‐AD dementia.ConclusionIn conclusion, our findings indicate that plasma Aβ42/40 and P‐tau217 could be useful in clinical practice, research and drug development as prognostic markers of future AD pathology.