Effects of storage conditions on the stability of blood-based markers for the diagnosis of Alzheimer’s disease

Abstract Objectives Alzheimer’s disease (AD) is considered the most common cause of dementia in older people. Recently, blood-based markers (BBM) Aβ1-42, Aβ1-40, and phospho Tau181 (p-Tau181) have demonstrated the potential to transform the diagnosis and prognostic assessment of AD. Our aim was to investigate the effect of different storage conditions on the quantification of these BBM and to evaluate the interchangeability of plasma and serum samples. Methods Forty-two individuals with some degree of cognitive impairment were studied. Thirty further patients were retrospectively selected. Aβ1-42, Aβ1-40, and p-Tau181 were quantified using the LUMIPULSE-G600II automated platform. To assess interchangeability between conditions, correction factors for magnitudes that showed strong correlations were calculated, followed by classification consistency studies. Results Storing samples at 4 °C for 8–9 days was associated with a decrease in Aβ fractions but not when stored for 1–2 days. Using the ratio partially attenuated the pre-analytical effects. For p-Tau181, samples stored at 4 °C presented lower concentrations, whereas frozen samples presented higher ones. Concerning classification consistency in comparisons that revealed strong correlations (p-Tau181), the percentage of total agreement was greater than 90 % in a large number of the tested cut-offs values. Conclusions Our findings provide relevant information for the standardization of sample collection and storage in the analysis of AD BBM in an automated platform. This knowledge is crucial to ensure their introduction into clinical settings.

[1]  M. Plebani,et al.  Pre-analytical variability of the Lumipulse immunoassay for plasma biomarkers of Alzheimer’s disease , 2022, Clinical chemistry and laboratory medicine.

[2]  M. Carrillo,et al.  The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease , 2022, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[3]  K. Blennow,et al.  Diagnostic value of serum versus plasma phospho-tau for Alzheimer’s disease , 2022, Alzheimer's research & therapy.

[4]  A. Lleó,et al.  Importance of cerebrospinal fluid storage conditions for the Alzheimer’s disease diagnostics on an automated platform , 2022, Clinical chemistry and laboratory medicine.

[5]  K. Blennow,et al.  Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview , 2021, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[6]  T. Vos,et al.  The estimation of the global prevalence of dementia from 1990‐2019 and forecasted prevalence through 2050: An analysis for the Global Burden of Disease (GBD) study 2019 , 2021, Alzheimer's & Dementia.

[7]  K. Blennow,et al.  Characterization of pre‐analytical sample handling effects on a panel of Alzheimer's disease–related blood‐based biomarkers: Results from the Standardization of Alzheimer's Blood Biomarkers (SABB) working group , 2021, Alzheimer's & dementia : the journal of the Alzheimer's Association.

[8]  K. Blennow,et al.  Head-to-Head Comparison of 8 Plasma Amyloid-β 42/40 Assays in Alzheimer Disease , 2021, JAMA neurology.

[9]  James G. Bollinger,et al.  The global Alzheimer's Association round robin study on plasma amyloid β methods , 2021, Alzheimer's & dementia.

[10]  K. Blennow,et al.  Effects of pre‐analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration , 2021, Alzheimer's & dementia.

[11]  Pei-Ning Wang,et al.  Effect of Times to Blood Processing on the Stability of Blood Proteins Associated with Dementia , 2020, Dementia and Geriatric Cognitive Disorders.

[12]  M. Chiu,et al.  Stability of Plasma Amyloid-β 1–40, Amyloid-β 1–42, and Total Tau Protein over Repeated Freeze/Thaw Cycles , 2020, Dementia and Geriatric Cognitive Disorders Extra.

[13]  L. Goldstein,et al.  Amyloid-β-independent regulators of tau pathology in Alzheimer disease , 2019, Nature Reviews Neuroscience.

[14]  Amanda Jiménez,et al.  The Sant Pau Initiative on Neurodegeneration (SPIN) cohort: A data set for biomarker discovery and validation in neurodegenerative disorders , 2019, Alzheimer's & dementia.

[15]  R. Batrla,et al.  Preanalytical sample handling recommendations for Alzheimer's disease plasma biomarkers , 2019, Alzheimer's & dementia.

[16]  J. Schott,et al.  Stability of blood-based biomarkers of Alzheimer's disease over multiple freeze-thaw cycles , 2018, Alzheimer's & dementia.

[17]  A. Fagan,et al.  The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis: A review , 2018, Alzheimer's & Dementia.

[18]  C. Jack,et al.  NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease , 2018, Alzheimer's & Dementia.

[19]  Linda J. C. van Waalwijk van Doorn,et al.  Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry , 2017, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[20]  Magda Tsolaki,et al.  Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases , 2015, Nature Reviews Neurology.

[21]  K. Blennow Dementia in 2010: Paving the way for Alzheimer disease drug development , 2011, Nature Reviews Neurology.