Dataset Information

Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview.

ABSTRACT:

Introduction

The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests.

Methods

We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients.

Results

The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis.

Discussion

This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD.

SUBMITTER: Delaby C

PROVIDER: S-EPMC9787404 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview.

Delaby Constance C Teunissen Charlotte E CE Blennow Kaj K Alcolea Daniel D Arisi Ivan I Amar Elodie Bouaziz EB Beaume Anne A Bedel Aurélie A Bellomo Giovanni G Bigot-Corbel Edith E Bjerke Maria M Blanc-Quintin Marie-Céline MC Boada Mercè M Bousiges Olivier O Chapman Miles D MD DeMarco Mari L ML D'Onofrio Mara M Dumurgier Julien J Dufour-Rainfray Diane D Engelborghs Sebastiaan S Esselmann Hermann H Fogli Anne A Gabelle Audrey A Galloni Elisabetta E Gondolf Clémentine C Grandhomme Frédérique F Grau-Rivera Oriol O Hart Melanie M Ikeuchi Takeshi T Jeromin Andreas A Kasuga Kensaku K Keshavan Ashvini A Khalil Michael M Körtvelyessy Peter P Kulczynska-Przybik Agnieszka A Laplanche Jean-Louis JL Lewczuk Piotr P Li Qiao-Xin QX Lleó Alberto A Malaplate Catherine C Marquié Marta M Masters Colin L CL Mroczko Barbara B Nogueira Léonor L Orellana Adelina A Otto Markus M Oudart Jean-Baptiste JB Paquet Claire C Paoletti Federico Paolini FP Parnetti Lucilla L Perret-Liaudet Armand A Peoc'h Katell K Poesen Koen K Puig-Pijoan Albert A Quadrio Isabelle I Quillard-Muraine Muriel M Rucheton Benoit B Schraen Susanna S Schott Jonathan M JM Shaw Leslie M LM Suárez-Calvet Marc M Tsolaki Magda M Tumani Hayrettin H Udeh-Momoh Chinedu T CT Vaudran Lucie L Verbeek Marcel M MM Verde Federico F Vermunt Lisa L Vogelgsang Jonathan J Wiltfang Jens J Zetterberg Henrik H Lehmann Sylvain S

Alzheimer's & dementia : the journal of the Alzheimer's Association 20211222 10

<h4>Introduction</h4>The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests.<h4>Methods</h4>We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed ...[more]

PMID: 34936194

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Project description:Widespread implementation of cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) in clinical settings requires improved accuracy for diagnosis of prodromal disease and for distinguishing AD from non-AD dementias. Novel and promising CSF biomarkers include neurogranin, a marker of synaptic degeneration, and YKL-40, a marker of neuroinflammation.CSF neurogranin and YKL-40 were measured in a cohort of 338 individuals including cognitively healthy controls and patients with stable mild cognitive impairment (sMCI), MCI who later developed AD (MCI-AD), AD dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and frontotemporal dementia (FTD). The diagnostic accuracy of neurogranin and YKL-40 were compared with the core AD biomarkers, β-amyloid (Aβ42 and Aβ40) and tau.Neurogranin levels were increased in AD and decreased in non-AD dementia compared with healthy controls. As a result, AD patients showed considerably higher CSF levels of neurogranin than DLB/PDD, VaD and FTD patients. CSF YKL-40 levels were increased in AD compared with DLB/PDD but not with VaD or FTD. Neither CSF neurogranin nor YKL-40 levels differed significantly between sMCI patients and MCI-AD patients. Both biomarkers correlated positively with CSF Aβ40 and tau. CSF neurogranin and YKL-40 could separate AD dementia from non-AD dementias (neurogranin, area under the curve [AUC] = 0.761; YKL-40, AUC = 0.604; Aβ42/neurogranin, AUC = 0.849; Aβ42/YKL-40, AUC = 0.785), but the diagnostic accuracy was not better compared to CSF Aβ and tau (Aβ42, AUC = 0.755; tau AUC = 0.858; Aβ42/tau, AUC = 0.895; Aβ42/Aβ40, AUC = 0.881). Similar results were obtained when separating sMCI from MCI-AD cases.CSF neurogranin and YKL-40 do not improve the diagnostic accuracy of either prodromal AD or AD dementia when compared to the core CSF AD biomarkers. Nevertheless, the CSF level of neurogranin is selectively increased in AD dementia, whereas YKL-40 is increased in both AD and FTD suggesting that synaptic degeneration and glial activation may be important in these neurodegenerative conditions.

Project description:Background18F-flortaucipir PET received FDA approval to visualize aggregated neurofibrillary tangles (NFTs) in brains of adult patients with cognitive impairment being evaluated for Alzheimer's disease (AD). However, manufacturer's guidelines for visual interpretation of 18F-flortaucipir PET differ from how 18F-flortaucipir PET has been measured in research settings using standardized uptake value ratios (SUVRs). How visual interpretation relates to 18F-flortaucipir PET SUVR, cerebrospinal fluid (CSF) biomarkers, or longitudinal clinical assessment is not well understood.ObjectiveWe compare various diagnostic methods in participants enrolled in longitudinal observational studies of aging and memory (n = 189, 23 were cognitively impaired).MethodsParticipants had tau PET, Aβ PET, MRI, and clinical and cognitive evaluation within 18 months (n = 189); the majority (n = 144) also underwent lumbar puncture. Two radiologists followed manufacturer's guidelines for 18F-flortaucipir PET visual interpretation.ResultsVisual interpretation had high agreement with SUVR (98.4%)and moderate agreement with CSF p-tau181 (86.1%). Two participants demonstrated 18F-flortaucipir uptake from meningiomas. Visual interpretation could not predict follow-up clinical assessment in 9.52% of cases.ConclusionVisual interpretation was highly consistent with SUVR (discordant participants had hemorrhagic infarcts or occipital-predominant AD NFT deposition) and moderately consistent with CSF p-tau181 (discordant participants had AD pathophysiology not detectable on tau PET). However, close association between AD NFT deposition and clinical onset in group-level studies does not necessarily hold at the individual level, with discrepancies arising from atypical AD, vascular dementia, or frontotemporal dementia. A better understanding of relationships across imaging, CSF biomarkers, and clinical assessment is needed to provide appropriate diagnoses for these individuals.

Dataset Information

Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview.

Introduction

Methods

Results

Discussion

Publications

Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview.

Similar Datasets

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