Plasma biomarkers across the Alzheimer’s disease continuum in the New Zealand‐Dementia Prevention Research Clinics

Abstract

AbstractBackgroundAdvances in ultra‐sensitive immunoassay methods, like Single molecule array (Simoa) technology, show that Alzheimer’s disease (AD) neuropathology can be detected in blood at the earliest stages of AD. This study compared cross‐sectional biomarker profiles for participants from the New Zealand‐Dementia Prevention Research Clinics (NZ‐DPRCs) who spanned the continuum from healthy older adults to a clinical diagnosis of AD.MethodBlood plasma samples were obtained from 253 NZ‐DPRC participants (aged 55 to 87) from their baseline assessment. Participants were classified as cognitively normal adults (CN, n = 34), subjective cognitive decline (SCD, n = 64), non‐amnestic mild cognitive impairment (single and multi‐domain, non‐aMCI, n = 23), amnestic MCI (single and multi‐domain, aMCI, n = 105), and AD (n = 27). Six plasma biomarkers were selected for quantification by the HD‐X Simoa analyser (Quanterix, Billerica, MA; University of Gothenburg, Sweden): AD biomarkers amyloid‐beta peptides (Aß1‐40; Aß1‐42) and phosphorylated tau species (p‐tau181; p‐tau231); neurofilament light (NfL), for general neuronal damage; and glial fibrillary acidic protein (GFAP), for astrocyte activation. Clinical, imaging and genetic demographic data were assessed in relation to the plasma biomarkers.ResultPlasma biomarkers across the five groups (figure 1) were assessed by linear regression adjusted for age and sex. P‐tau181, p‐tau231, GFAP and NfL were natural log‐transformed to approximate normality and improve homogeneity of variance. Biomarkers p‐tau181, p‐tau231, GFAP, NfL, Aß1‐42/Aß1‐40 ratio and Aß1‐42, all showed group effects (P < 0.05; Aß1‐40, p<0.08). Tukey’s HSD post‐hoc test for pairwise group comparisons showed significant differences in GFAP for AD vs CN, SCD, non‐aMCI as well as SCD vs MCI (P < 0.05); p‐tau181 for AD vs CN and SCD (P < 0.05); p‐tau231 for AD vs non‐aMCI (P < 0.05); Aß1‐42 for aMCI vs CN and SCD (P < 0.05); Aß1‐42/Aß1‐40 ratio for SCD vs aMCI (P < 0.05). ROC analysis will be reported for the diagnostic accuracy of these blood analytes.ConclusionSimoa‐quantitated blood biomarkers in the NZ‐DPRC cohort differentiates clinical groups spanning the AD continuum cross‐sectionally.