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 language | English |
|---|---|
| Pages (from-to) | 764-775 |
| Number of pages | 12 |
| Journal | Alzheimer's and Dementia |
| Volume | 15 |
| Issue number | 6 |
| DOIs | |
| State | Published - 1 Jun 2019 |
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Keywords
- Alzheimer's disease
- Amyloid PET
- Classification and regression trees (CART)
- Machine learning
- Plasma amyloid β
- Simoa immunoassay
- Subjective memory complainers
Cite this
}
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 journal › Article
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 - Benda, Norbert
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 -