Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer’s disease

Abstract

Background The recent promise of disease-modifying therapies for Alzheimer’s disease (AD) has reinforced the need for accurate biomarkers for early disease detection, diagnosis and treatment monitoring. Advances in the development of novel blood-based biomarkers for AD have revealed that plasma levels of tau phosphorylated at various residues are specific and sensitive to AD dementia. However, the currently available tests have shortcomings in access, throughput, and scalability that limit widespread implementation. Methods We evaluated the diagnostic and prognostic performance of a high-throughput and fully-automated Lumipulse plasma p-tau181 assay for the detection of AD. Plasma from older clinically unimpaired individuals (CU, n = 463) and patients with mild cognitive impairment (MCI, n = 107) or AD dementia (n = 78) were obtained from the longitudinal Stanford University Alzheimer’s Disease Research Center (ADRC) and the Stanford Aging and Memory Study (SAMS) cohorts. We evaluated the discriminative accuracy of plasma p-tau181 for clinical AD diagnosis, association with amyloid β peptides and p-tau181 concentrations in CSF, association with amyloid positron emission tomography (PET), and ability to predict longitudinal cognitive and functional change. Results The assay showed robust performance in differentiating AD from control participants (AUC 0.959, CI: 0.912 to 0.990), and was strongly associated with CSF p-tau181, CSF Aβ42/Aβ40 ratio, and amyloid-PET global SUVRs. Associations between plasma p-tau181 with CSF biomarkers were significant when examined separately in Aβ+ and Aβ− groups. Plasma p-tau181 significantly increased over time in CU and AD diagnostic groups. After controlling for clinical diagnosis, age, sex, and education, baseline plasma p-tau181 predicted change in MoCA overall and change in CDR Sum of Boxes in the AD group over follow-up of up to 5 years. Conclusions This fully-automated and available blood-based biomarker assay therefore may be useful for early detection, diagnosis, prognosis, and treatment monitoring of AD.

Diagnostic performance of plasma Aβ1-42, Aβ1-40and pTau181in the LUMIPULSE automated platform for the detection of Alzheimer disease

“…The accuracy of pTau 181 in plasma has been previously studied in the Lumipulse and different accuracies have been reported to differentiate CU from AD. While Janelidze et al reported an AUC of 0.7 [17] Wilson et al found an accuracy of 0.96 [24]. In our study, we found a global accuracy of 0.91 for pTau 181 .…”

“…The performance of plasma markers to discriminate patients with AD from cognitively unimpaired participants, patients with other dementias and with not degenerative dementias has been assessed in previous studies using other analytical platforms, with AUCs ranging from 0.70 to 0.96 for pTau 181 [7,17,[23][24][25][26][27], and from 0.64 to 0.86 for Aβ 1-/Aβ 1-40 [5,8,10]. Most of the studies reported better accuracies with the use of composite measures that combined two or more markers and/or clinical or genetic information.…”

Relationship between baseline plasma p‐tau181 and longitudinal changes in cognition and structural brain measures in a cohort of cognitively unimpaired older adults

“…Moreover, it has been reported that plasma p‐tau181 levels might indicate AD pathology even before Aβ biomarkers reach the positivity threshold 34,35 . However, most studies have relied on longer follow‐up periods (over 2 years) when evaluating the relationship between plasma p‐tau181 and cognitive or structural brain outcomes 6,24,36 . Our null findings suggest that plasma p‐tau181 might correlate with these measures later in the disease process.…”

“…34,35 However, most studies have relied on longer followup periods (over 2 years) when evaluating the relationship between plasma p-tau181 and cognitive or structural brain outcomes. 6,24,36 Our null findings suggest that plasma p-tau181 might correlate with these measures later in the disease process. In addition, sample Some of the previous studies have investigated the relationship between plasma p-tau181 and cognitive performance in cohorts of CU older adults with a higher risk of developing AD, for example, cohorts originating from memory clinics and enriched with APOE ε4 carriers or with evidence of subjective cognitive decline (SCD) at baseline.…”

Post‐translational modifications linked to preclinical Alzheimer's disease–related pathological and cognitive changes

“…Separate aliquots processed by the Lumipulse G system (Fujirebio US, Inc., Malvern, PA) were used to measure CSF levels of AD biomarkers (phosphorylated tau 181 [p-tau 181 ], Aβ 42 , and Aβ 40 ) for all 147 SAMS CU and 89 of the 111 ADRC+ participants. 29 The remaining…”