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

Alzheimers Dement. 2022 Aug;18(8):1484-1497. doi: 10.1002/alz.12510. Epub 2021 Nov 29.


Introduction: Pre-analytical sample handling might affect the results of Alzheimer's disease blood-based biomarkers. We empirically tested variations of common blood collection and handling procedures.

Methods: We created sample sets that address the effect of blood collection tube type, and of ethylene diamine tetraacetic acid plasma delayed centrifugation, centrifugation temperature, aliquot volume, delayed storage, and freeze-thawing. We measured amyloid beta (Aβ)42 and 40 peptides with six assays, and Aβ oligomerization-tendency (OAβ), amyloid precursor protein (APP)699-711 , glial fibrillary acidic protein (GFAP), neurofilament light (NfL), total tau (t-tau), and phosphorylated tau181.

Results: Collection tube type resulted in different values of all assessed markers. Delayed plasma centrifugation and storage affected Aβ and t-tau; t-tau was additionally affected by centrifugation temperature. The other markers were resistant to handling variations.

Discussion: We constructed a standardized operating procedure for plasma handling, to facilitate introduction of blood-based biomarkers into the research and clinical settings.

Keywords: Alzheimer's disease; amyloid beta; plasma biomarkers; pre-analytics; stability; tau.

Publication types

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

MeSH terms

  • Alzheimer Disease*
  • Amyloid beta-Peptides
  • Biomarkers
  • Blood Group Antigens*
  • Humans
  • Reference Standards
  • Specimen Handling
  • tau Proteins


  • Amyloid beta-Peptides
  • Biomarkers
  • Blood Group Antigens
  • tau Proteins