Plasma biomarkers of amyloid, tau, astrogliosis, and axonal injury in a mixed memory clinic cohort

INTRODUCTION: Studies have shown that blood biomarkers can differentiate dementia disorders. However, the diagnosis of dementia still relies primarily on cerebrospinal fluid and imaging modalities. The new disease-modifying treatments call for more widely applicable biomarkers.

METHODS: Plasma samples (n = 250) from two mixed memory clinic were included. Participants were divided into amyloid beta positives (Aβ+) and Aβ negatives (Aβ-). Plasma phosphorylated tau (p-tau) 181, p-tau231, Aβ1-42 (Aβ42), Aβ40, Aβ42/Aβ40, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were measured by single molecule array.

RESULTS: Significant differences were found among cognitively unimpaired, mild cognitive impairment, Alzheimer's disease (AD), and non-AD, and nearly all of the biomarkers were able to predict amyloid status. When combining p-tau181 and p-tau231 they predicted Aβ positivity with an area under the curve (AUC) of 0.75, and when combining all biomarkers an AUC of 0.86 was found.

DISCUSSION: This study supports previous findings on plasma biomarkers, even when investigated in a typical clinical setting in a consecutive, heterogeneous, mixed memory clinic.

HIGHLIGHTS: This study investigated seven plasma biomarkers in a mixed memory clinic, regardless of amyloid co-pathology or atypical phenotypes.These findings support previous promising results on plasma biomarkers, even when investigated in a heterogeneous population.The combination of phosphorylated tau (p-tau)181 and p-231 performed only slightly worse than a panel of multiple biomarkers, aligning with previous studies.Plasma biomarkers show potential for future applications in primary care, treatment monitoring, and trial selection.