%0 Journal Article %J J Alzheimers Dis %D 2016 %T Comparison of Different Matrices as Potential Quality Control Samples for Neurochemical Dementia Diagnostics. %A Lelental, Natalia %A Brandner, Sebastian %A Kofanova, Olga %A Blennow, Kaj %A Zetterberg, Henrik %A Andreasson, Ulf %A Engelborghs, Sebastiaan %A Mroczko, Barbara %A Gabryelewicz, Tomasz %A Teunissen, Charlotte %A Mollenhauer, Brit %A Parnetti, Lucilla %A Chiasserini, Davide %A Molinuevo, José Luis %A Perret-Liaudet, Armand %A Verbeek, Marcel M %A Andreasen, Niels %A Brosseron, Frederic %A Bahl, Justyna M C %A Herukka, Sanna-Kaisa %A Hausner, Lucrezia %A Frölich, Lutz %A Labonte, Anne %A Poirier, Judes %A Miller, Anne-Marie %A Zilka, Norbert %A Kovacech, Branislav %A Urbani, Andrea %A Suardi, Silvia %A Oliveira, Catarina %A Baldeiras, Ines %A Dubois, Bruno %A Rot, Uros %A Lehmann, Sylvain %A Skinningsrud, Anders %A Betsou, Fay %A Wiltfang, Jens %A Gkatzima, Olymbia %A Winblad, Bengt %A Buchfelder, Michael %A Kornhuber, Johannes %A Lewczuk, Piotr %K Amyloid beta-Peptides %K Animals %K Anti-Bacterial Agents %K Biomarkers %K Cattle %K Clinical Chemistry Tests %K Dementia %K Humans %K Peptide Fragments %K Quality Control %K Reference Standards %K Serum Albumin, Bovine %K Sodium Azide %K tau Proteins %K Time Factors %K Tissue Preservation %X

BACKGROUND: Assay-vendor independent quality control (QC) samples for neurochemical dementia diagnostics (NDD) biomarkers are so far commercially unavailable. This requires that NDD laboratories prepare their own QC samples, for example by pooling leftover cerebrospinal fluid (CSF) samples.

OBJECTIVE: To prepare and test alternative matrices for QC samples that could facilitate intra- and inter-laboratory QC of the NDD biomarkers.

METHODS: Three matrices were validated in this study: (A) human pooled CSF, (B) Aβ peptides spiked into human prediluted plasma, and (C) Aβ peptides spiked into solution of bovine serum albumin in phosphate-buffered saline. All matrices were tested also after supplementation with an antibacterial agent (sodium azide). We analyzed short- and long-term stability of the biomarkers with ELISA and chemiluminescence (Fujirebio Europe, MSD, IBL International), and performed an inter-laboratory variability study.

RESULTS: NDD biomarkers turned out to be stable in almost all samples stored at the tested conditions for up to 14 days as well as in samples stored deep-frozen (at - 80°C) for up to one year. Sodium azide did not influence biomarker stability. Inter-center variability of the samples sent at room temperature (pooled CSF, freeze-dried CSF, and four artificial matrices) was comparable to the results obtained on deep-frozen samples in other large-scale projects.

CONCLUSION: Our results suggest that it is possible to replace self-made, CSF-based QC samples with large-scale volumes of QC materials prepared with artificial peptides and matrices. This would greatly facilitate intra- and inter-laboratory QC schedules for NDD measurements.

%B J Alzheimers Dis %V 52 %P 51-64 %8 2016 03 01 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/26967210?dopt=Abstract %R 10.3233/JAD-150883 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Diagnostic Impact of Cerebrospinal Fluid Biomarker (Pre-)Analytical Variability in Alzheimer's Disease. %A Niemantsverdriet, Ellis %A Goossens, Joery %A Struyfs, Hanne %A Martin, Jean-Jacques %A Goeman, Johan %A De Deyn, Peter Paul %A Vanderstichele, Hugo %A Engelborghs, Sebastiaan %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Amyloid beta-Peptides %K Autopsy %K Cognitive Dysfunction %K Enzyme-Linked Immunosorbent Assay %K Exercise %K Female %K Follow-Up Studies %K Humans %K Male %K Middle Aged %K Peptide Fragments %K Psychiatric Status Rating Scales %K Retrospective Studies %K Statistics, Nonparametric %K tau Proteins %X

Intra- and inter-laboratory variability of cerebrospinal fluid (CSF) biomarker analyses remains an important issue. We investigated the clinical-diagnostic impact of CSF biomarker concentration shifts in mild cognitive impairment (MCI) and autopsy-confirmed Alzheimer's disease (AD) dementia patients. MCI patients (n = 85), autopsy-confirmed AD dementia patients (n = 72), and cognitively healthy controls (n = 100) were included in this prospective, longitudinal study. AD dementia patients were followed up until death, and controls were included from 1992 until 2003. In-house validated cutoff values of biomarkers were applied: Aβ1-42 <638.5 pg/mL, T-tau>296.5 pg/mL, P-tau(181P) >56.5 pg/mL. Both increments and decrements (from ± 5% to ± 40% ) were added to the true (=observed) CSF biomarker values, imitating the anticipated differences in biomarker concentrations. Within certain limits, the clinical diagnostic performance of AD CSF biomarkers remains largely unchanged and clinical diagnostic accuracy deviated less than 8.2% from the reference when concentration shifts ranging between -20% and +20% were added to one of the three CSF biomarkers in MCI and autopsy-confirmed AD patients. Notwithstanding the fact that (pre- and post-)analytical parameters can affect the clinical classification, the present exploratory study provides evidence that for a specific context of use, the impact on clinical accuracy of biomarker concentration shifts might be lower than originally expected. In conclusion, induced shifts of ±20% in only one of the three biomarkers has limited impact on the clinical accuracy of AD CSF biomarkers in MCI and autopsy-confirmed AD patients when using the IWG-2 criteria.

%B J Alzheimers Dis %V 51 %P 97-106 %8 2016 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/26836187?dopt=Abstract %R 10.3233/JAD-150953 %0 Journal Article %J Lancet Neurol %D 2014 %T Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. %A Dubois, Bruno %A Feldman, Howard H %A Jacova, Claudia %A Hampel, Harald %A Molinuevo, José Luis %A Blennow, Kaj %A DeKosky, Steven T %A Gauthier, Serge %A Selkoe, Dennis %A Bateman, Randall %A Cappa, Stefano %A Crutch, Sebastian %A Engelborghs, Sebastiaan %A Frisoni, Giovanni B %A Fox, Nick C %A Galasko, Douglas %A Habert, Marie-Odile %A Jicha, Gregory A %A Nordberg, Agneta %A Pasquier, Florence %A Rabinovici, Gil %A Robert, Philippe %A Rowe, Christopher %A Salloway, Stephen %A Sarazin, Marie %A Epelbaum, Stéphane %A de Souza, Leonardo C %A Vellas, Bruno %A Visser, Pieter J %A Schneider, Lon %A Stern, Yaakov %A Scheltens, Philip %A Cummings, Jeffrey L %K Alzheimer Disease %K Biomarkers %K Humans %K International Cooperation %K Phenotype %K Practice Guidelines as Topic %K Societies, Medical %X

In the past 8 years, both the International Working Group (IWG) and the US National Institute on Aging-Alzheimer's Association have contributed criteria for the diagnosis of Alzheimer's disease (AD) that better define clinical phenotypes and integrate biomarkers into the diagnostic process, covering the full staging of the disease. This Position Paper considers the strengths and limitations of the IWG research diagnostic criteria and proposes advances to improve the diagnostic framework. On the basis of these refinements, the diagnosis of AD can be simplified, requiring the presence of an appropriate clinical AD phenotype (typical or atypical) and a pathophysiological biomarker consistent with the presence of Alzheimer's pathology. We propose that downstream topographical biomarkers of the disease, such as volumetric MRI and fluorodeoxyglucose PET, might better serve in the measurement and monitoring of the course of disease. This paper also elaborates on the specific diagnostic criteria for atypical forms of AD, for mixed AD, and for the preclinical states of AD.

%B Lancet Neurol %V 13 %P 614-29 %8 2014 Jun %G eng %N 6 %1 http://www.ncbi.nlm.nih.gov/pubmed/24849862?dopt=Abstract %R 10.1016/S1474-4422(14)70090-0