TY - JOUR
T1 - Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer’s disease
AU - Wilson, Edward N.
AU - Young, Christina B.
AU - Ramos Benitez, Javier
AU - Swarovski, Michelle S.
AU - Feinstein, Igor
AU - Vandijck, Manu
AU - Le Guen, Yann
AU - Kasireddy, Nandita M.
AU - Shahid, Marian
AU - Corso, Nicole K.
AU - Wang, Qian
AU - Kennedy, Gabriel
AU - Trelle, Alexandra N.
AU - Lind, Betty
AU - Channappa, Divya
AU - Belnap, Malia
AU - Ramirez, Veronica
AU - Skylar-Scott, Irina
AU - Younes, Kyan
AU - Yutsis, Maya V.
AU - Le Bastard, Nathalie
AU - Quinn, Joseph F.
AU - van Dyck, Christopher H.
AU - Nairn, Angus
AU - Fredericks, Carolyn A.
AU - Tian, Lu
AU - Kerchner, Geoffrey A.
AU - Montine, Thomas J.
AU - Sha, Sharon J.
AU - Davidzon, Guido
AU - Henderson, Victor W.
AU - Longo, Frank M.
AU - Greicius, Michael D.
AU - Wagner, Anthony D.
AU - Wyss-Coray, Tony
AU - Poston, Kathleen L.
AU - Mormino, Elizabeth C.
AU - Andreasson, Katrin I.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Biomarkers
KW - Phospho-tau
KW - Plasma
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U2 - 10.1186/s13195-022-01116-2
DO - 10.1186/s13195-022-01116-2
M3 - Article
C2 - 36371232
AN - SCOPUS:85141708651
SN - 1758-9193
VL - 14
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 1
M1 - 172
ER -