Evaluating the diagnostic performance of six plasma biomarkers for Alzheimer’s disease and other neurodegenerative dementias in a large Chinese cohort

BACKGROUND: Ethnic variations and detection methods may lead to differences in diagnostic biomarkers of dementia, and few comparative studies have evaluated the six plasma biomarkers of Alzheimer's disease (AD) and other neurodegenerative dementias in the Chinese population. METHODS: A cross-sectional cohort of 668 participants were enrolled, including 245 amnesic mild cognitive impairment (aMCI) or AD patients with Aβ positive pathology, 67 with frontotemporal dementia (FTD), 100 with progressive supranuclear palsy (PSP), 72 with dementia with Lewy bodies (DLB) and 184 healthy controls. Additionally, a longitudinal subset of 19 aMCI and 30 AD patients was followed for an average period of 1 year. Plasma biomarkers, including p-tau181, p-tau217, p-tau231, NfL, GFAP, and α-synuclein, were simultaneously measured using a novel single molecular array method. Aβ42 and p-tau181 levels in CSF, amyloid PET and structural MRI were measured. RESULTS: Plasma p-tau217 and p-tau231 were most effective in diagnosing aMCI/AD (AUC = 0.95 and 0.93, respectively), while p-tau217, p-tau231 and p-tau181 presented the best differential diagnosis for AD from PSP, FTD and DLB respectively (AUC = 0.84, 0.81 and 0.83). α-synuclein was presented as the best biomarker for PSP variant and behavior variant FTD subtypes (AUC = 0.81 and 0.74, respectively). Among them, p-tau217, p-tau231, GFAP and a-synuclein were negatively correlated with CSF Aβ42/40, while p-tau217 and GFAP were positively correlated with CSF p-tau181. Besides, p-tau181, p-tau217, and GFAP were associated with temporal lobe volume, while p-tau231 and GFAP were associated with frontal lobe volume. Longitudinal analysis showed the higher p-tau181 could predict the cognitive decline progression. CONCLUSIONS: This study validate the practicality of blood biomarkers in the Chinese Han population using a novel single molecule immune detection method. Through the clinical performance study for several biomarkers, we found the plasma p-tau217 was the most effective biomarker in AD diagnosis, and p-tau showed high accuracy for differential diagnosis of AD from other dementia, GFAP is associated with multiple aspects of AD pathology, and frontal and temporal lobe volume, and p-tau181 can reflect the dynamic cognitive decline of AD.