Carla R Schubert1, Adam J Paulsen1, A Alex Pinto1, Natascha Merten2, Karen J Cruickshanks1,2. 1. Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA. 2. Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
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.
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.
Entities:
Keywords:
Alzheimer’s disease; amyloid-β; blood biomarkers; epidemiology; neurofilament light; plasma; serum; single molecule array; total tau
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