Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Definition of a threshold on the plasma Aβ42/Aβ40 ratio measured by single-molecule array to predict the amyloid status of individuals without dementia

Lise Colmant
* ORCID logo ,
Emilien Boyer
* ,
Thomas Gerard
,
Kristel Sleegers
,
Renaud Lhommel
ORCID logo ,
Adrian Ivanoiu
,
Philippe Lefèvre
,
Pascal Kienlen-Campard
ORCID logo ,
Bernard Hanseeuw
Version 1 : Received: 18 December 2023 / Approved: 19 December 2023 / Online: 19 December 2023 (10:19:53 CET)

A peer-reviewed article of this Preprint also exists.

Colmant, L.; Boyer, E.; Gerard, T.; Sleegers, K.; Lhommel, R.; Ivanoiu, A.; Lefèvre, P.; Kienlen-Campard, P.; Hanseeuw, B. Definition of a Threshold for the Plasma Aβ42/Aβ40 Ratio Measured by Single-Molecule Array to Predict the Amyloid Status of Individuals without Dementia. Int. J. Mol. Sci. 2024, 25, 1173. Colmant, L.; Boyer, E.; Gerard, T.; Sleegers, K.; Lhommel, R.; Ivanoiu, A.; Lefèvre, P.; Kienlen-Campard, P.; Hanseeuw, B. Definition of a Threshold for the Plasma Aβ42/Aβ40 Ratio Measured by Single-Molecule Array to Predict the Amyloid Status of Individuals without Dementia. Int. J. Mol. Sci. 2024, 25, 1173.

Abstract

Alzheimer's disease (AD) is characterized by abnormal amyloid beta (Aβ) plaques and hyperphosphorylated tau in the brain. Aβ plaques precede cognitive impairments and can be detected through amyloid-PET or in cerebrospinal fluid (CSF). Assessing the plasma Aβ42/Aβ40 ratio seems promising for non-invasive and cost-effective detection of brain Aβ accumulation. This approach involves some challenges, including the accuracy of blood-based biomarker measurements and the establishment of clear, standardized thresholds to categorize the risk of developing brain amyloid pathology. Plasma Aβ42/Aβ40 ratio was measured in 277 volunteers without dementia, 70 AD patients and 18 non-AD patients using single-molecule array. Patients (n=88) and some volunteers (n=66) were subject to evaluation of amyloid status by CSF Aβ quantification or PET analysis. Thresholds of plasma Aβ42/Aβ40 ratio were determined based on a Gaussian mixture model, a decision tree, and the Youden index. The 0.0472 threshold, the one with the highest sensitivity, was retained for general population without dementia screening, and the 0.0450 threshold was retained for research and clinical trials recruitment, aiming to minimize the need for CSF or PET analyses to identify amyloid-positive individuals. These findings offer a promising step towards a cost-effective method for identifying individuals at risk of developing AD.

Keywords

Alzheimer’s disease 1; plasma amyloid 2; SIMOA 3; plasma Aβ42/Aβ40 ratio 4; amyloid prediction 5; biomarkers 6; Alzheimer’s disease screening 7

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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