Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease

INSIGHT-preAD Study Group, Alzheimer Precision Medicine Initiative (APMI)

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Introduction: Blood-based biomarkers of pathophysiological brain amyloid β (Aβ) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management. Methods: We investigated whether plasma concentrations of the Aβ1–40/Aβ1–42 ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain Aβ positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-a-priori hypothesis study using machine learning. Results: The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5% and 81%, respectively, for the plasma Aβ1–40/Aβ1–42 ratio. The accuracy is not affected by the apolipoprotein E (APOE)ε4 allele, sex, or age. Discussion: Our results encourage an independent validation cohort study to confirm the indication that the plasma Aβ1–40/Aβ1–42 ratio, assessed via Simoa, may improve future standard of care and clinical trial design.

Original languageEnglish
Pages (from-to)764-775
Number of pages12
JournalAlzheimer's and Dementia
Volume15
Issue number6
DOIs
StatePublished - 1 Jun 2019

Fingerprint

Amyloid
Alzheimer Disease
Clinical Trials
Apolipoprotein E4
Validation Studies
Brain
Standard of Care
Immunoassay
ROC Curve
Positron-Emission Tomography
Cohort Studies
Biomarkers
Alleles
Amyloid angiopathy
Machine Learning

Keywords

  • Alzheimer's disease
  • Amyloid PET
  • Classification and regression trees (CART)
  • Machine learning
  • Plasma amyloid β
  • Simoa immunoassay
  • Subjective memory complainers

Cite this

INSIGHT-preAD Study Group ; Alzheimer Precision Medicine Initiative (APMI). / Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease. In: Alzheimer's and Dementia. 2019 ; Vol. 15, No. 6. pp. 764-775.
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title = "Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease",
abstract = "Introduction: Blood-based biomarkers of pathophysiological brain amyloid β (Aβ) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management. Methods: We investigated whether plasma concentrations of the Aβ1–40/Aβ1–42 ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain Aβ positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-a-priori hypothesis study using machine learning. Results: The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5{\%} and 81{\%}, respectively, for the plasma Aβ1–40/Aβ1–42 ratio. The accuracy is not affected by the apolipoprotein E (APOE)ε4 allele, sex, or age. Discussion: Our results encourage an independent validation cohort study to confirm the indication that the plasma Aβ1–40/Aβ1–42 ratio, assessed via Simoa, may improve future standard of care and clinical trial design.",
keywords = "Alzheimer's disease, Amyloid PET, Classification and regression trees (CART), Machine learning, Plasma amyloid β, Simoa immunoassay, Subjective memory complainers",
author = "{INSIGHT-preAD Study Group} and {Alzheimer Precision Medicine Initiative (APMI)} and Andrea Vergallo and Lucile M{\'e}gret and Simone Lista and Enrica Cavedo and Henrik Zetterberg and Kaj Blennow and Eugeen Vanmechelen and {De Vos}, Ann and Habert, {Marie Odile} and Potier, {Marie Claude} and Bruno Dubois and Christian Neri and Harald Hampel and H. Bakardjian and H. Benali and H. Bertin and J. Bonheur and L. Boukadida and N. Boukerrou and E. Cavedo and P. Chiesa and O. Colliot and B. Dubois and M. Dubois and S. Epelbaum and G. Gagliardi and R. Genthon and Habert, {M. O.} and H. Hampel and M. Houot and A. Kas and F. Lamari and M. Levy and S. Lista and C. Metzinger and F. Mochel and F. Nyasse and C. Poisson and M. Revillon and A. Santos and Andrade, {K. S.} and M. Sole and M. Surtee and {de Schotten M}, Thiebaud and A. Vergallo and N. Younsi and Aguilar, {Lisi Flores} and Claudio Babiloni and Filippo Baldacci and Sidney O'Bryant",
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Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease. / INSIGHT-preAD Study Group; Alzheimer Precision Medicine Initiative (APMI).

In: Alzheimer's and Dementia, Vol. 15, No. 6, 01.06.2019, p. 764-775.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Plasma amyloid β 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease

AU - INSIGHT-preAD Study Group

AU - Alzheimer Precision Medicine Initiative (APMI)

AU - Vergallo, Andrea

AU - Mégret, Lucile

AU - Lista, Simone

AU - Cavedo, Enrica

AU - Zetterberg, Henrik

AU - Blennow, Kaj

AU - Vanmechelen, Eugeen

AU - De Vos, Ann

AU - Habert, Marie Odile

AU - Potier, Marie Claude

AU - Dubois, Bruno

AU - Neri, Christian

AU - Hampel, Harald

AU - Bakardjian, H.

AU - Benali, H.

AU - Bertin, H.

AU - Bonheur, J.

AU - Boukadida, L.

AU - Boukerrou, N.

AU - Cavedo, E.

AU - Chiesa, P.

AU - Colliot, O.

AU - Dubois, B.

AU - Dubois, M.

AU - Epelbaum, S.

AU - Gagliardi, G.

AU - Genthon, R.

AU - Habert, M. O.

AU - Hampel, H.

AU - Houot, M.

AU - Kas, A.

AU - Lamari, F.

AU - Levy, M.

AU - Lista, S.

AU - Metzinger, C.

AU - Mochel, F.

AU - Nyasse, F.

AU - Poisson, C.

AU - Revillon, M.

AU - Santos, A.

AU - Andrade, K. S.

AU - Sole, M.

AU - Surtee, M.

AU - de Schotten M, Thiebaud

AU - Vergallo, A.

AU - Younsi, N.

AU - Aguilar, Lisi Flores

AU - Babiloni, Claudio

AU - Baldacci, Filippo

AU - O'Bryant, Sidney

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Introduction: Blood-based biomarkers of pathophysiological brain amyloid β (Aβ) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management. Methods: We investigated whether plasma concentrations of the Aβ1–40/Aβ1–42 ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain Aβ positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-a-priori hypothesis study using machine learning. Results: The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5% and 81%, respectively, for the plasma Aβ1–40/Aβ1–42 ratio. The accuracy is not affected by the apolipoprotein E (APOE)ε4 allele, sex, or age. Discussion: Our results encourage an independent validation cohort study to confirm the indication that the plasma Aβ1–40/Aβ1–42 ratio, assessed via Simoa, may improve future standard of care and clinical trial design.

AB - Introduction: Blood-based biomarkers of pathophysiological brain amyloid β (Aβ) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management. Methods: We investigated whether plasma concentrations of the Aβ1–40/Aβ1–42 ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain Aβ positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-a-priori hypothesis study using machine learning. Results: The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5% and 81%, respectively, for the plasma Aβ1–40/Aβ1–42 ratio. The accuracy is not affected by the apolipoprotein E (APOE)ε4 allele, sex, or age. Discussion: Our results encourage an independent validation cohort study to confirm the indication that the plasma Aβ1–40/Aβ1–42 ratio, assessed via Simoa, may improve future standard of care and clinical trial design.

KW - Alzheimer's disease

KW - Amyloid PET

KW - Classification and regression trees (CART)

KW - Machine learning

KW - Plasma amyloid β

KW - Simoa immunoassay

KW - Subjective memory complainers

UR - http://www.scopus.com/inward/record.url?scp=85065799769&partnerID=8YFLogxK

U2 - 10.1016/j.jalz.2019.03.009

DO - 10.1016/j.jalz.2019.03.009

M3 - Article

C2 - 31113759

AN - SCOPUS:85065799769

VL - 15

SP - 764

EP - 775

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

IS - 6

ER -