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An accurate fully automated panel of plasma biomarkers for Alzheimer's disease

Palmqvist, Sebastian LU orcid ; Stomrud, Erik LU ; Cullen, Nicholas LU ; Janelidze, Shorena LU ; Manuilova, Ekaterina ; Jethwa, Alexander ; Bittner, Tobias ; Eichenlaub, Udo ; Suridjan, Ivonne and Kollmorgen, Gwendlyn , et al. (2022) In Alzheimer's and Dementia
Abstract

Introduction: There is a great need for fully automated plasma assays that can measure amyloid beta (Aβ) pathology and predict future Alzheimer's disease (AD) dementia. Methods: Two cohorts (n = 920) were examined: Panel A+ (n = 32 cognitively unimpaired [CU], n = 106 mild cognitive impairment [MCI], and n = 89 AD) and BioFINDER-1 (n = 461 CU, n = 232 MCI). Plasma Aβ42/Aβ40, phosphorylated tau (p-tau)181, two p-tau217 variants, ApoE4 protein, neurofilament light, and GFAP were measured using Elecsys prototype immunoassays. Results: The best biomarker for discriminating Aβ-positive versus Aβ-negative participants was Aβ42/Aβ40 (are under the curve [AUC] 0.83–0.87). Combining Aβ42/Aβ40, p-tau181, and ApoE4 improved the AUCs significantly... (More)

Introduction: There is a great need for fully automated plasma assays that can measure amyloid beta (Aβ) pathology and predict future Alzheimer's disease (AD) dementia. Methods: Two cohorts (n = 920) were examined: Panel A+ (n = 32 cognitively unimpaired [CU], n = 106 mild cognitive impairment [MCI], and n = 89 AD) and BioFINDER-1 (n = 461 CU, n = 232 MCI). Plasma Aβ42/Aβ40, phosphorylated tau (p-tau)181, two p-tau217 variants, ApoE4 protein, neurofilament light, and GFAP were measured using Elecsys prototype immunoassays. Results: The best biomarker for discriminating Aβ-positive versus Aβ-negative participants was Aβ42/Aβ40 (are under the curve [AUC] 0.83–0.87). Combining Aβ42/Aβ40, p-tau181, and ApoE4 improved the AUCs significantly (0.90 to 0.93; P< 0.01). Adding additional biomarkers had marginal effects (ΔAUC ≤0.01). In BioFINDER, p-tau181, p-tau217, and ApoE4 predicted AD dementia within 6 years in CU (AUC 0.88) and p-tau181, p-tau217, and Aβ42/Aβ40 in MCI (AUC 0.87). Discussion: The high accuracies for Aβ pathology and future AD dementia using fully automated instruments are promising for implementing plasma biomarkers in clinical trials and clinical routine.

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type
Contribution to journal
publication status
in press
subject
keywords
Alzheimer's disease, amyloid beta, apolipoprotein E, area under the curve, blood, cerebrospinal fluid, clinical practice, cognitively unimpaired, diagnostics, Elecsys, fully automated instruments, glial fibrillary acidic protein, immunoassays, implementation, mild cognitive impairment, neurofilament light, phosphorylated tau, plasma, prediction, prognostics
in
Alzheimer's and Dementia
publisher
Wiley
external identifiers
  • pmid:35950735
  • scopus:85135827045
ISSN
1552-5260
DOI
10.1002/alz.12751
language
English
LU publication?
yes
id
f8f6b96d-c24b-46c6-9ae9-9c6e301f076c
date added to LUP
2022-11-29 13:17:45
date last changed
2023-01-22 08:51:31
@article{f8f6b96d-c24b-46c6-9ae9-9c6e301f076c,
  abstract     = {{<p>Introduction: There is a great need for fully automated plasma assays that can measure amyloid beta (Aβ) pathology and predict future Alzheimer's disease (AD) dementia. Methods: Two cohorts (n = 920) were examined: Panel A+ (n = 32 cognitively unimpaired [CU], n = 106 mild cognitive impairment [MCI], and n = 89 AD) and BioFINDER-1 (n = 461 CU, n = 232 MCI). Plasma Aβ42/Aβ40, phosphorylated tau (p-tau)181, two p-tau217 variants, ApoE4 protein, neurofilament light, and GFAP were measured using Elecsys prototype immunoassays. Results: The best biomarker for discriminating Aβ-positive versus Aβ-negative participants was Aβ42/Aβ40 (are under the curve [AUC] 0.83–0.87). Combining Aβ42/Aβ40, p-tau181, and ApoE4 improved the AUCs significantly (0.90 to 0.93; P&lt; 0.01). Adding additional biomarkers had marginal effects (ΔAUC ≤0.01). In BioFINDER, p-tau181, p-tau217, and ApoE4 predicted AD dementia within 6 years in CU (AUC 0.88) and p-tau181, p-tau217, and Aβ42/Aβ40 in MCI (AUC 0.87). Discussion: The high accuracies for Aβ pathology and future AD dementia using fully automated instruments are promising for implementing plasma biomarkers in clinical trials and clinical routine.</p>}},
  author       = {{Palmqvist, Sebastian and Stomrud, Erik and Cullen, Nicholas and Janelidze, Shorena and Manuilova, Ekaterina and Jethwa, Alexander and Bittner, Tobias and Eichenlaub, Udo and Suridjan, Ivonne and Kollmorgen, Gwendlyn and Riepe, Matthias and von Arnim, Christine A.F. and Tumani, Hayrettin and Hager, Klaus and Heidenreich, Fedor and Mattsson-Carlgren, Niklas and Zetterberg, Henrik and Blennow, Kaj and Hansson, Oskar}},
  issn         = {{1552-5260}},
  keywords     = {{Alzheimer's disease; amyloid beta; apolipoprotein E; area under the curve; blood; cerebrospinal fluid; clinical practice; cognitively unimpaired; diagnostics; Elecsys; fully automated instruments; glial fibrillary acidic protein; immunoassays; implementation; mild cognitive impairment; neurofilament light; phosphorylated tau; plasma; prediction; prognostics}},
  language     = {{eng}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{An accurate fully automated panel of plasma biomarkers for Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1002/alz.12751}},
  doi          = {{10.1002/alz.12751}},
  year         = {{2022}},
}