José Luis Molinuevo1, Kaj Blennow2, Bruno Dubois3, Sebastiaan Engelborghs4, Piotr Lewczuk5, Armand Perret-Liaudet6, Charlotte E Teunissen7, Lucilla Parnetti8. 1. Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic i Universitari, IDIBAPS and Barcelona Beta Research Centre, Pasqual Maragall Foundation, Barcelona, Spain. Electronic address: JLMOLI@clinic.ub.es. 2. Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 3. Centre des Maladies Cognitives et Comportementales, Hôpital de la Salpêtrière, AP-HP, Institute of Brain and Spinal Cord (ICM), UMR-S975, Université Pierre et Marie Curie-Paris 6, Paris, France. 4. Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA), Middelheim and Hoge Beuken, Antwerp, Belgium; Reference Centre for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Antwerp, Belgium. 5. Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen and Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany. 6. Centre for Memory Resources and Research (CMRR), Neurobiology Laboratory, GHE, Hôpitaux de Lyon, Université Lyon 1, CNRS UMR5292, INSERM U1028, Lyon, France. 7. Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands. 8. Centre for Memory Disturbances and Alzheimer's Centre, Section of Neurology, University of Perugia, Perugia, Italy.
Abstract
BACKGROUND: Cerebrospinal fluid (CSF) biomarkers β-amyloid 1-42 (Aβ1-42), also expressed as Aβ1-42:Aβ1-40 ratio, T-tau, and P-tau181P, have proven diagnostic accuracy for mild cognitive impairment and Alzheimer's disease (AD). How to use, interpret, and disclose biomarker results drives the need for standardization. METHODS: Previous Alzheimer's Biomarkers Standardization Initiative meetings discussed preanalytical issues affecting Aβ1-42 and tau in CSF. This second round of consensus meetings focused on issues related to clinical use of AD CSF biomarkers. RESULTS: Consensus was reached that lumbar puncture for AD CSF biomarker analysis be considered as a routine clinical test in patients with early-onset dementia, at the prodromal stage or with atypical AD. Moreover, consensus was reached on which biomarkers to use, how results should be interpreted, and potential confounding factors. CONCLUSIONS: Changes in Aβ1-42, T-tau, and P-tau181P allow diagnosis of AD in its prodromal stage. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up.
BACKGROUND: Cerebrospinal fluid (CSF) biomarkers β-amyloid 1-42 (Aβ1-42), also expressed as Aβ1-42:Aβ1-40 ratio, T-tau, and P-tau181P, have proven diagnostic accuracy for mild cognitive impairment and Alzheimer's disease (AD). How to use, interpret, and disclose biomarker results drives the need for standardization. METHODS: Previous Alzheimer's Biomarkers Standardization Initiative meetings discussed preanalytical issues affecting Aβ1-42 and tau in CSF. This second round of consensus meetings focused on issues related to clinical use of AD CSF biomarkers. RESULTS: Consensus was reached that lumbar puncture for AD CSF biomarker analysis be considered as a routine clinical test in patients with early-onset dementia, at the prodromal stage or with atypical AD. Moreover, consensus was reached on which biomarkers to use, how results should be interpreted, and potential confounding factors. CONCLUSIONS: Changes in Aβ1-42, T-tau, and P-tau181P allow diagnosis of AD in its prodromal stage. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up.
Authors: Laura A Rabin; Colette M Smart; Paul K Crane; Rebecca E Amariglio; Lorin M Berman; Mercé Boada; Rachel F Buckley; Gaël Chételat; Bruno Dubois; Kathryn A Ellis; Katherine A Gifford; Angela L Jefferson; Frank Jessen; Mindy J Katz; Richard B Lipton; Tobias Luck; Paul Maruff; Michelle M Mielke; José Luis Molinuevo; Farnia Naeem; Audrey Perrotin; Ronald C Petersen; Lorena Rami; Barry Reisberg; Dorene M Rentz; Steffi G Riedel-Heller; Shannon L Risacher; Octavio Rodriguez; Perminder S Sachdev; Andrew J Saykin; Melissa J Slavin; Beth E Snitz; Reisa A Sperling; Caroline Tandetnik; Wiesje M van der Flier; Michael Wagner; Steffen Wolfsgruber; Sietske A M Sikkes Journal: J Alzheimers Dis Date: 2015-09-24 Impact factor: 4.472
Authors: Suzanne E Schindler; Courtney L Sutphen; Charlotte Teunissen; Lena M McCue; John C Morris; David M Holtzman; Sandra D Mulder; Philip Scheltens; Chengjie Xiong; Anne M Fagan Journal: Alzheimers Dement Date: 2017-07-12 Impact factor: 21.566