Recommendations to Standardize Preanalytical Confounding Factors in Alzheimer’s and Parkinson’s Disease Cerebrospinal Fluid Biomarkers: An Update
Abstract
Early diagnosis of neurodegenerative disorders such as Alzheimer's (AD) or Parkinson's disease (PD) is needed to slow down or halt the disease at the earliest stage. Cerebrospinal fluid (CSF) biomarkers can be a good tool for early diagnosis. However, their use in clinical practice is challenging due to the high variability found between centers in the concentrations of both AD CSF biomarkers (Aβ42, total tau and phosphorylated tau) and PD CSF biomarker (α-synuclein). Such a variability has been partially attributed to different preanalytical procedures between laboratories, thus highlighting the need to establish standardized operating procedures. Here, we merge two previous consensus guidelines for preanalytical confounding factors in order to achieve one exhaustive guideline updated with new evidence for Aβ42, total tau and phosphorylated tau, and α-synuclein. The proposed standardized operating procedures are applicable not only to novel CSF biomarkers in AD and PD, but also to biomarkers for other neurodegenerative disorders.
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Preanalytical aspects and development of standard operating procedures for sample handling and analysis, such as for AD biomarkers in CSF and blood, and quality control programs, are a requirement for in vitro diagnostic tests.
“This especially applies to preanalytical aspects and the development of standard operating procedures for sample handling and analysis, such as for AD biomarkers in CSF and blood, 141 — 144 and to quality control programs, 145 which are a requirement for in vitro diagnostic tests.”
From New developments of biofluid‐based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia (2022) · cites this paper as [141]
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- Authors
- del Campo, M., Mollenhauer, B., Bertolotto, A., Engelborghs, S., Hampel, H., Simonsen, A. H., Kapaki, E., Kruse, N., Le Bastard, N., Lehmann, S., Molinuevo, J. L., Parnetti, L., Perret-Liaudet, A., Sáez-Valero, J., Saka, E., Urbani, A., Vanmechelen, E., Verbeek, M., Visser, P. J., & Teunissen, C.
- Affiliations
- Department of Clinical Chemistry, Neurology Laboratory, VU University medical center (VUmc), Room PK1 Br016, De Boelelaan 1117, 1081 HV,Amsterdam,The Netherlands.
- Universitätsmedizin Göttingen (DE)
- Ospedale San Luigi Gonzaga (IT)
- University of Antwerp (BE)
- Goethe University Frankfurt (DE)
- Copenhagen University Hospital (DK)
- National and Kapodistrian University of Athens (GR)
- Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium
- Inserm (FR)
- Alzheimer‘s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clinic, Barcelona, Spain
- University of Perugia (IT)
- Neurobiologie, CMRR, Gériatrie, Hospices Civils de Lyon, Université Lyon 1 – CNRS UMR5292 – INSERM - U1028, Lyon, France and Société Française de Biologie Clinique (SFBC), France
- Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d‘Alacant, Spain and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain
- Hacettepe University Hospital (TR)
- University of Rome Tor Vergata (IT)
- ADx NeuroSciences (BE)
- Radboud University Nijmegen (NL)
- Maastricht University (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- ORCID
- Venue
- Biomarkers in Medicine
- Publisher
- Informa UK Limited
- Published
- 2012-08
- Volume
- 6
- Issue
- 4
- Pages
- 419-430
- ISSN
- 1752-0363 (ISSN-L)
- 1752-0371
- OpenAlex
- W2139778458
- Cited by
- 343
- References
- 65
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 22 · 2023: 21 · 2022: 34 · 2021: 36 · 2020: 32 · 2019: 33 · 2018: 28 · 2017: 22 · 2016: 17 · 2015: 43 · 2014: 18 · 2013: 11
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomarkers in Medicine (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- GRO (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Dutch Research Council
- Topics
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- cerebrospinal fluid biomarkers, Alzheimer's disease, Parkinson's disease, amyloid-beta 42, total tau, phosphorylated tau, alpha-synuclein, standard operating procedures, inter-laboratory variability, neurodegenerative diseases, early diagnosis
- MeSH terms
- Alzheimer Disease, Humans, Parkinson Disease, Peptide Fragments, Specimen Handling, Temperature, Biomarkers, Amyloid beta-Peptides, tau Proteins, Phase Transition, alpha-Synuclein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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