Effect of Long-Term Storage on the Reliability of Blood Biomarkers for Alzheimer's Disease and Neurodegeneration

J Alzheimers Dis. 2022;85(3):1021-1029. doi: 10.3233/JAD-215096.

Abstract

Background: Stored blood samples from longitudinal cohort studies may be useful for studying biomarkers of preclinical Alzheimer's disease.

Objective: This study aimed to determine the reliability of amyloid-β40 and amyloid-β42 (Aβ40, Aβ42), total tau (TTau), and neurofilament light (NfL) concentrations measured in blood samples stored long-term at -80°C.

Methods: Aβ40, Aβ42, TTau, and NfL were measured in serum and plasma samples from two longitudinal cohort studies. Serum samples had been stored at -80°C for 5 (n = 24), 14 (n = 24), and 20 years (N = 78) and plasma samples had been stored for 16 years (N = 78). Biomarker concentrations were measured in duplicate using a single molecule array assay (Simoa; Quanterix, Billerica, MA). Replicate samples for each sample type and storage length were included.

Results: The concentrations of Aβ40, Aβ42, TTau, and NfL were within expected ranges. Some serum TTau concentrations were below the limit of detection. The average intra-assay coefficients of variation (CV) for duplicate measures were 2-7% for all assays except for serum TTau, which were higher (CVs 13% and 17%). Mean differences in original replicate pair Aβ40, Aβ42, and NfL concentrations were slightly greater in samples stored for longer versus shorter time periods.

Conclusion: Aβ40, Aβ42, TTau, and NfL can be measured in serum and plasma samples that have been stored up to 20 years at -80°C. Long-term storage may be associated with small increases in the variability of concentrations in samples stored 14 or more years.

Keywords: Alzheimer’s disease; amyloid-β; blood biomarkers; epidemiology; neurofilament light; plasma; serum; single molecule array; total tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Amyloid beta-Peptides / blood*
  • Biomarkers / blood*
  • Blood Specimen Collection
  • Cohort Studies
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neurofilament Proteins / blood
  • Peptide Fragments
  • Reproducibility of Results
  • Specimen Handling*
  • Temperature*
  • Time Factors

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Neurofilament Proteins
  • Peptide Fragments
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)