학술논문

Definition of a Threshold for the Plasma Aβ42/Aβ40 Ratio Measured by Single-Molecule Array to Predict the Amyloid Status of Individuals without Dementia
Document Type
article
Source
International Journal of Molecular Sciences, Vol 25, Iss 2, p 1173 (2024)
Subject
Alzheimer’s disease
plasma amyloid
SIMOA
plasma Aβ42/Aβ40 ratio
amyloid prediction
biomarkers
Biology (General)
QH301-705.5
Chemistry
QD1-999
Language
English
ISSN
1422-0067
1661-6596
Abstract
Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) plaques and hyperphosphorylated tau in the brain. Aβ plaques precede cognitive impairments and can be detected through amyloid-positron emission tomography (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’s 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.