A novel ultrasensitive assay for plasma p-tau217: performance in individuals with subjective cognitive decline and early Alzheimer’s disease

Abstract

INTRODUCTIONDetection of Alzheimer’s disease (AD) pathophysiology among cognitively unimpaired individuals and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma p-tau217 is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited.METHODSWe employed a novel p-tau217 immunoassay (UGOT p-tau217) in four independent cohorts (n=308) including a cerebrospinal fluid (CSF) biomarker-classified cohort (Discovery), two cohorts consisting mostly of cognitively unimpaired participants (MYHAT and Pittsburgh), and a population-based cohort of individuals with SCD (β-AARC).RESULTSUGOT p-tau217 showed high accuracy (AUC= 0.80-0.91) identifying Aβ pathology, determined either by Aβ positron emission tomography or CSF Aβ42/40 ratio. In individuals experiencing SCD, UGOT p-tau217 showed high accuracy identifying those with a positive CSF Aβ42/40 ratio (AUC= 0.91).DISCUSSIONUGOT p-tau217 can be an easily accessible and efficient way to screen and monitor patients with suspected AD pathophysiology, even in the early stages of the continuum.

Plasma p-tau217 in Alzheimer’s disease: Lumipulse and ALZpath SIMOA head-to-head comparison

“…These results are consistent with the greater fold change of p-tau217 compared to other p-tau species, namely p-tau231 and p-tau181 recently demonstrated. 4,5,[10][11][12][13][14][15][16] Of note, the cutoffs resulting in the highest Youden index in the ROC analyses for discriminating AD versus NDD and controls resulted in very similar cutoff values across assays, suggesting the possible adoption of a single value for AD diagnosis, ideally to be established by multi-centre validation studies. The head-to-head comparison with ALZpath p-tau217 showed a slightly higher fold-change for Lumipulse with a comparable discrimination accuracy compared to SIMOA, even in the subcohort of MCI subjects at earlier stages of the disease.…”

“…[5][6][7][8][9] To date, phosphorylated tau at threonine 217 (p-tau217) appeared to be one of the most sensitive and specific AD markers compared to other phosphorylated tau species for differentiating AD from other neurodegenerative disorders. 6,[10][11][12][13][14][15][16] In addition, p-tau217 exhibits a unique longitudinal trajectory in preclinical AD amyloid-positive individuals, with increases over time being significantly associated with worsening cortical atrophy and declining cognitive performance. 4,6,13,17,18 Most published studies focusing on p-tau species have used immunoassays on either the Meso Scale Discovery (MSD) or SIMOA platforms.…”

“…4,6,13,17,18 Most published studies focusing on p-tau species have used immunoassays on either the Meso Scale Discovery (MSD) or SIMOA platforms. 5,10,11,15,19 The recent development of similar assays using chemiluminescent enzyme immunoassay (CLEIA) technology (including the fully automated Lumipulse platform) represents an attractive further step for their easier use and wider consistent applicability in clinical practice. The fully automation produces more consistent results between laboratories, and overtime in the same laboratory.…”

Aggregation of gold nanoclusters in amyloid fibers: a luminescence assay for amyloid fibrillation detection and inhibitor screening

“…The related studies indicate that the detection of amyloid fibrils commonly occurs in cerebrospinal fluid or human plasma. [42][43][44][45] It appears that the detection of lysozyme fibrosis can exclude interferences from metal ions, amylase, bovine serum albumin (BSA), human serum albumin, alkaline phosphatase, trypsin, DNA and RNA, as described in the literature. 28,46 On the basis of the response of the Au NCs to the fibers, we applied Au NCs to the detection of lysozyme amyloid fibrillation.…”

Plasma p-tau212: antemortem diagnostic performance and prediction of autopsy verification of Alzheimer’s disease neuropathology

“…al method 36 . Plasma p-tau217 was measured using a published and validated in-house assay 31 . Samples were analyzed in singlicates while internal quality controls (iQC) samples measured at the start and the end of each technical run were used to monitor reproducibility.…”