Development of amyloid β (1-42) certified reference material NMIJ CRM 6210-a

Area of Science:

• Biomarker Development
• Metrology
• Analytical Chemistry

Background:

• Amyloid beta (Aβ) is a critical biomarker for Alzheimer's disease (AD).
• Standardized measurement methods are essential for reliable Aβ quantification.
• Metrological traceability is crucial for assessing the equivalence of Aβ measurements.

Purpose of the Study:

• To develop a certified reference material (CRM) for amyloid beta (Aβ).
• To establish metrological traceability of Aβ concentration to the International System of Units (SI).
• To ensure accurate and comparable quantification of Aβ in diagnostic assays.

Main Methods:

• Development of a lyophilized synthetic peptide CRM (NMIJ CRM 6210-a) containing Aβ (1-42) and its modified forms.
• Quantification of total Aβ and native Aβ using amino acid analysis with isotope-dilution mass spectrometry (IDMS).
• Determination of Aβ content within the total Aβ mixture via liquid chromatography with ultraviolet detection (LC-UV).

Main Results:

• Certified values assigned for total Aβ mass concentration ((46 ± 11) mg/L) and Aβ mass concentration ((42.6 ± 7.0) mg/L).
• Traceability to SI units established through rigorous analytical methods.
• Demonstrated stability of the CRM during storage and use.

Conclusions:

• The developed CRM provides SI-traceable quantification of amyloid beta.
• This CRM supports accurate Alzheimer's disease biomarker assessment.
• The CRM enhances inter-laboratory comparability for amyloid beta measurements.