Highly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease

Abstract Plasma biomarkers that reflect specific amyloid beta (Abeta) proteoforms provide an insight in the treatment effects of Alzheimer’s disease (AD) therapies. Our aim was to develop and validate ready-to-use Simoa ‘Amyblood’ assays that measure full length Abeta1-42 and Abeta1-40 and compare t...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Elisabeth H. Thijssen, Inge M. W. Verberk, Jeroen Vanbrabant, Anne Koelewijn, Hans Heijst, Philip Scheltens, Wiesje van der Flier, Hugo Vanderstichele, Erik Stoops, Charlotte E. Teunissen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/783c572408a54a5796b786b326983e7c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:783c572408a54a5796b786b326983e7c
record_format	dspace
spelling	oai:doaj.org-article:783c572408a54a5796b786b326983e7c2021-12-02T14:49:43ZHighly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease10.1038/s41598-021-89004-x2045-2322https://doaj.org/article/783c572408a54a5796b786b326983e7c2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89004-xhttps://doaj.org/toc/2045-2322Abstract Plasma biomarkers that reflect specific amyloid beta (Abeta) proteoforms provide an insight in the treatment effects of Alzheimer’s disease (AD) therapies. Our aim was to develop and validate ready-to-use Simoa ‘Amyblood’ assays that measure full length Abeta1-42 and Abeta1-40 and compare their performance with two commercial assays. Linearity, intra- and inter-assay %CV were compared between Amyblood, Quanterix Simoa triplex, and Euroimmun ELISA. Sensitivity and selectivity were assessed for Amyblood and the Quanterix triplex. Clinical performance was assessed in CSF biomarker confirmed AD (n = 43, 68 ± 6 years) and controls (n = 42, 62 ± 5 years). Prototype and Amyblood showed similar calibrator curves and differentiation (20 AD vs 20 controls, p < 0.001). Amyblood, Quanterix triplex, and ELISA showed similar linearity (96%-122%) and intra-assay %CVs (≤ 3.1%). A minor non-specific signal was measured with Amyblood of + 2.4 pg/mL Abeta1-42 when incubated with 60 pg/mL Abeta1-40. A substantial non-specific signal of + 24.7 pg/mL Abetax-42 was obtained when 40 pg/mL Abeta3-42 was measured with the Quanterix triplex. Selectivity for Abeta1-42 at physiological Abeta1-42 and Abeta1-40 concentrations was 125% for Amyblood and 163% for Quanterix. Amyblood and Quanterix ratios (p < 0.001) and ELISA Abeta1-42 concentration (p = 0.025) could differentiate AD from controls. We successfully developed and upscaled a prototype to the Amyblood assays with similar technical and clinical performance as the Quanterix triplex and ELISA, but better specificity and selectivity than the Quanterix triplex assay. These results suggest leverage of this specific assay for monitoring treatment response in trials.Elisabeth H. ThijssenInge M. W. VerberkJeroen VanbrabantAnne KoelewijnHans HeijstPhilip ScheltensWiesje van der FlierHugo VandersticheleErik StoopsCharlotte E. TeunissenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elisabeth H. Thijssen Inge M. W. Verberk Jeroen Vanbrabant Anne Koelewijn Hans Heijst Philip Scheltens Wiesje van der Flier Hugo Vanderstichele Erik Stoops Charlotte E. Teunissen Highly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease
description	Abstract Plasma biomarkers that reflect specific amyloid beta (Abeta) proteoforms provide an insight in the treatment effects of Alzheimer’s disease (AD) therapies. Our aim was to develop and validate ready-to-use Simoa ‘Amyblood’ assays that measure full length Abeta1-42 and Abeta1-40 and compare their performance with two commercial assays. Linearity, intra- and inter-assay %CV were compared between Amyblood, Quanterix Simoa triplex, and Euroimmun ELISA. Sensitivity and selectivity were assessed for Amyblood and the Quanterix triplex. Clinical performance was assessed in CSF biomarker confirmed AD (n = 43, 68 ± 6 years) and controls (n = 42, 62 ± 5 years). Prototype and Amyblood showed similar calibrator curves and differentiation (20 AD vs 20 controls, p < 0.001). Amyblood, Quanterix triplex, and ELISA showed similar linearity (96%-122%) and intra-assay %CVs (≤ 3.1%). A minor non-specific signal was measured with Amyblood of + 2.4 pg/mL Abeta1-42 when incubated with 60 pg/mL Abeta1-40. A substantial non-specific signal of + 24.7 pg/mL Abetax-42 was obtained when 40 pg/mL Abeta3-42 was measured with the Quanterix triplex. Selectivity for Abeta1-42 at physiological Abeta1-42 and Abeta1-40 concentrations was 125% for Amyblood and 163% for Quanterix. Amyblood and Quanterix ratios (p < 0.001) and ELISA Abeta1-42 concentration (p = 0.025) could differentiate AD from controls. We successfully developed and upscaled a prototype to the Amyblood assays with similar technical and clinical performance as the Quanterix triplex and ELISA, but better specificity and selectivity than the Quanterix triplex assay. These results suggest leverage of this specific assay for monitoring treatment response in trials.
format	article
author	Elisabeth H. Thijssen Inge M. W. Verberk Jeroen Vanbrabant Anne Koelewijn Hans Heijst Philip Scheltens Wiesje van der Flier Hugo Vanderstichele Erik Stoops Charlotte E. Teunissen
author_facet	Elisabeth H. Thijssen Inge M. W. Verberk Jeroen Vanbrabant Anne Koelewijn Hans Heijst Philip Scheltens Wiesje van der Flier Hugo Vanderstichele Erik Stoops Charlotte E. Teunissen
author_sort	Elisabeth H. Thijssen
title	Highly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease
title_short	Highly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease
title_full	Highly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease
title_fullStr	Highly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease
title_full_unstemmed	Highly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease
title_sort	highly specific and ultrasensitive plasma test detects abeta(1–42) and abeta(1–40) in alzheimer’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/783c572408a54a5796b786b326983e7c
work_keys_str_mv	AT elisabethhthijssen highlyspecificandultrasensitiveplasmatestdetectsabeta142andabeta140inalzheimersdisease AT ingemwverberk highlyspecificandultrasensitiveplasmatestdetectsabeta142andabeta140inalzheimersdisease AT jeroenvanbrabant highlyspecificandultrasensitiveplasmatestdetectsabeta142andabeta140inalzheimersdisease AT annekoelewijn highlyspecificandultrasensitiveplasmatestdetectsabeta142andabeta140inalzheimersdisease AT hansheijst highlyspecificandultrasensitiveplasmatestdetectsabeta142andabeta140inalzheimersdisease AT philipscheltens highlyspecificandultrasensitiveplasmatestdetectsabeta142andabeta140inalzheimersdisease AT wiesjevanderflier highlyspecificandultrasensitiveplasmatestdetectsabeta142andabeta140inalzheimersdisease AT hugovanderstichele highlyspecificandultrasensitiveplasmatestdetectsabeta142andabeta140inalzheimersdisease AT erikstoops highlyspecificandultrasensitiveplasmatestdetectsabeta142andabeta140inalzheimersdisease AT charlotteeteunissen highlyspecificandultrasensitiveplasmatestdetectsabeta142andabeta140inalzheimersdisease
_version_	1718389454710767616

Highly specific and ultrasensitive plasma test detects Abeta(1–42) and Abeta(1–40) in Alzheimer’s disease

Ejemplares similares