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Articles by Maria C. Carrillo
Total Records ( 21 ) for Maria C. Carrillo
  Maria C. Carrillo , Andrew Blackwell , Harald Hampel , Johan Lindborg , Reisa Sperling , Dale Schenk , Jeffrey J. Sevigny , Steven Ferris , David A. Bennett , Suzanne Craft , Timothy Hsu and William Klunk
  The purpose of the Alzheimer's Association Research Roundtable meeting was to discuss the potential of finding diagnostic tools to determine the earliest risk factors for Alzheimer's disease (AD). Currently, drugs approved for AD address symptoms which are generally manifest after the disease is already well-established, but there is a growing pipeline of drugs that may alter the underlying pathology and therefore slow or halt progression of the disease. As these drugs become available, it will become increasingly imperative that those at risk for AD be detected and possibly treated early, especially given recent indications that the disease process may start decades before the first clinical symptoms are recognized. Early detection must go hand-in-hand with qualified tools to determine the efficacy of drugs in people who may be asymptomatic or who have only very mild symptoms of the disease. Devising strategies and screening tools to identify and monitor those at risk in order to perform ”prevention” trials is seen by many as a top public-health priority, made all the more urgent by an impending growth in the elderly population worldwide.
  Maria C. Carrillo , Charles A. Sanders and Russell G. Katz
  The Alzheimer's Disease Neuroimaging Initiative is the largest public-private partnership on brain research underway at the National Institutes of Health. This 6-year study tracks cognitive and brain changes in normal subjects, those with mild cognitive impairment, and individuals with Alzheimer's disease. It was designed to provide better tools for performing effective clinical trials, and is slated to run until 2010. While data are being generated and analyzed, researchers involved in the study are developing an extension, i.e., the Alzheimer's Disease Neuroimaging Initiative II. The Foundation for the National Institutes of Health and the Alzheimer's Association convened a meeting to review the progress, evaluate future directions, and obtain the United States Food and Drug Administration's perspective on how the Alzheimer's Disease Neuroimaging Initiative could affect the drug-approval process.
  Ronald Black , Barry Greenberg , J. Michael Ryan , Holly Posner , Jeffrey Seeburger , Joan Amatniek , Malca Resnick , Richard Mohs , David S. Miller , Daniel Saumier , Maria C. Carrillo and Yaakov Stern
  The assessment of patient outcomes in clinical trials of new therapeutics for Alzheimer's disease (AD) continues to evolve. In addition to assessing drugs for symptomatic relief, an increasing number of trials are focusing on potential disease-modifying agents. Moreover, participants with AD are being studied earlier in their course of disease. As a result, the limitations of current outcome measures have become more apparent, as has the need for better instruments. In recognition of the need to review and possibly revise current assessment measures, the Alzheimer's Association, in cooperation with industry leaders and academic investigators, convened a Research Roundtable meeting devoted to scales as outcome measures for AD clinical trials. The meeting included a discussion of methodological issues in the use of scales in AD clinical trials, including cross-cultural issues. Specific topics related to the use of cognitive, functional, global, and neuropsychiatric scales were also presented. Speakers also addressed academic and industry initiatives for pooling data from untreated and placebo-treated patients in clinical trials. A number of regulatory topics were also discussed with agency representatives. Panel discussions highlighted areas of controversy, in an effort to gain consensus on various topics.
  Maria C. Carrillo , Eric Dishman and Tim Plowman
  The Everyday Technologies for Alzheimer's Care initiative was launched by the Alzheimer's Association and Intel Corporation in 2003 to identify and fund promising research in the use of technology–especially information and communication technologies–for monitoring, diagnosing, and treating Alzheimer's disease. At the last two progress meetings, scientific leaders of the two partners, together with aging health technology academic scientists, met to review the most recent research and discuss how current and developing technologies can address growing needs in Alzheimer care.
  Zaven S. Khachaturian , Ronald C. Petersen , Peter J. Snyder , Ara S. Khachaturian , Paul Aisen , Mony de Leon , Barry D. Greenberg , Walter Kukull , Paul Maruff , Reisa A. Sperling , Yaakov Stern , Jacques Touchon , Bruno Vellas , Sandrine Andrieu , Michael W. Weiner , Maria C. Carrillo and Lisa J. Bain
  The fourth Leon Thal Symposium (LTS2010) was convened in Toulouse, France, on November 3, 2010. This symposium reviewed design parameters that are necessary to develop comprehensive national databases on healthy aging. Such datasets offer the potential to serve as the foundation for a systems-approach to solve the dual public health problems of: (1) early detection of people who are at elevated risk for Alzheimer‘s disease, and (2) the development of interventions to delay onset of, or prevent, late-life dementia. The symposium considered three interrelated components of a National Database for Longitudinal Studies on Healthy Aging as follows: (a) a registry of healthy aging adults; (b) refined computer-based assessments for data gathering, including assessments of behavioral/memory changes associated with aging that are appropriate for broad use in nonexpert settings; and (c) high performance computing/supercomputer-based approaches for health data modeling and mining
  Rachelle S. Doody , Patricia E. Cole , David S. Miller , Eric Siemers , Ronald Black , Howard Feldman , Rachel Schindler , Stephen Graham , Theresa Heath , Ara S. Khachaturian , Rebecca Evans and Maria C. Carrillo
  The number of clinical trials for Alzheimer‘s disease conducted outside the United States in a broad array of countries is increasing. As the number of compounds ready for clinical testing increases, and as trials become longer and more complex, this trend is expected to grow. The cultural and ethical context of global clinical trials, potential benefits for those involved, and practical approaches to obstacles generated by these global trials were discussed at a meeting of the Alzheimer‘s Association Research Roundtable. Regulatory issues, including regional differences in study registration procedures, rules for collecting and reporting serious adverse events, requirements for national identity of study populations, and regulatory audits were also discussed by individuals who are knowledgeable about global clinical trials for Alzheimer‘s disease.
  Clifford R. Jack , Marilyn S. Albert , David S. Knopman , Guy M. McKhann , Reisa A. Sperling , Maria C. Carrillo , Bill Thies and Creighton H. Phelps
  Background Criteria for the clinical diagnosis of Alzheimer's disease (AD) were established in 1984. A broad consensus now exists that these criteria should be revised to incorporate state-of-the-art scientific knowledge. Methods The National Institute on Aging (NIA) and the Alzheimer's Association sponsored a series of advisory round table meetings in 2009 whose purpose was to establish a process for revising diagnostic and research criteria for AD. The recommendation from these advisory meetings was that three separate work groups should be formed with each assigned the task of formulating diagnostic criteria for one phase of the disease: the dementia phase; the symptomatic, pre-dementia phase; and the asymptomatic, preclinical phase of AD. Results Two notable differences from the AD criteria published in 1984 are incorporation of biomarkers of the underlying disease state and formalization of different stages of disease in the diagnostic criteria. There was a broad consensus within all three workgroups that much additional work is needed to validate the application of biomarkers for diagnostic purposes. In the revised NIA-Alzheimer's Association criteria, a semantic and conceptual distinction is made between AD pathophysiological processes and clinically observable syndromes that result, whereas this distinction was blurred in the 1984 criteria. Conclusions The new criteria for AD are presented in three documents. The core clinical criteria of the recommendations regarding AD dementia and MCI due to AD are intended to guide diagnosis in the clinical setting. However, the recommendations of the preclinical AD workgroup are intended purely for research purposes.
  Guy M. McKhann , David S. Knopman , Howard Chertkow , Howard Chertkow , Clifford R. Jack , Claudia H. Kawas , William E. Klunk , Walter J. Koroshetz , Jennifer J. Manly , Richard Mayeux , Richard C. Mohs , John C. Morris , Martin N. Rossor , Philip Scheltens , Maria C. Carrillo , Bill Thies , Sandra Weintraub and Creighton H. Phelps
  The National Institute on Aging and the Alzheimer‘s Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer‘s disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.
  Reisa A. Sperling , Paul S. Aisen , Laurel A. Beckett , Laurel A. Beckett , Suzanne Craft , Anne M. Fagan , Takeshi Iwatsubo , Clifford R. Jack , Jeffrey Kaye , Thomas J. Montine , Denise C. Park , Eric M. Reiman , Christopher C. Rowe , Eric Siemers , Yaakov Stern , Yaakov Stern , Maria C. Carrillo , Bill Thies , Marcelle Morrison- Bogorad , Molly V. Wagster and Creighton H. Phelps
  The National Institute on Aging and the Alzheimer‘s Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer‘s disease (AD), referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings.
  Reisa A. Sperling , Clifford R. Jack , Sandra E. Black , Matthew P. Frosch , Steven M. Greenberg , Bradley T. Hyman , Philip Scheltens , Maria C. Carrillo , William Thies , Martin M. Bednar , Ronald S. Black , H. Robert Brashear , Michael Grundman , Eric R. Siemers , Howard H. Feldman and Rachel J. Schindler
  Amyloid imaging related abnormalities (ARIA) have now been reported in clinical trials with multiple therapeutic avenues to lower amyloid-β burden in Alzheimer‘s disease (AD). In response to concerns raised by the Food and Drug Administration, the Alzheimer‘s Association Research Roundtable convened a working group to review the publicly available trial data, attempts at developing animal models, and the literature on the natural history and pathology of related conditions. The spectrum of ARIA includes signal hyperintensities on fluid attenuation inversion recoverysequences thought to represent ”vasogenic edema“ and/or sulcal effusion (ARIA-E), as well as signal hypointensities on GRE/T2∗ thought to represent hemosiderin deposits (ARIA-H), including microhemorrhage and superficial siderosis. The etiology of ARIA remains unclear but the prevailing data support vascular amyloid as a common pathophysiological mechanism leading to increased vascular permeability. The workgroup proposes recommendations for the detection and monitoring of ARIA in ongoing AD clinical trials, as well as directions for future research.
  Niklas Mattsson , Ulf Andreasson , Staffan Persson , Hiroyuki Arai , Sat Dev Batish , Sergio Bernardini , Luisella Bocchio- Chiavetto , Marinus A. Blankenstein , Maria C. Carrillo , Sonia Chalbot , Els Coart , Davide Chiasserini , Neal Cutler , Gunilla Dahlfors , Stefan Duller , Anne M. Fagan , Orestes Forlenza , Giovanni B. Frisoni , Douglas Galasko , Daniela Galimberti , Harald Hampel , Aase Handberg , Michael T. Heneka , Adrianna Z. Herskovits , Sanna-Kaisa Herukka , David M. Holtzman , Christian Humpel , Bradley T. Hyman , Khalid Iqbal , Khalid Iqbal , Stephan A. Kaeser , Elmar Kaiser , Elisabeth Kapaki , Daniel Kidd , Peter Klivenyi , Cindy S. Knudsen , Markus P. Kummer , James Lui , Albert Llado , Piotr Lewczuk , Qiao-Xin Li , Ralph Martins , Colin Masters , John McAuliffe , Marc Mercken , Abhay Moghekar , Jose Luis Molinuevo , Thomas J. Montine , William Nowatzke , Richard O’Brien , Markus Otto , George P. Paraskevas , Lucilla Parnetti , Ronald C. Petersen , David Prvulovic , Herman P.M. de Reus , Robert A. Rissman , Elio Scarpini , Alessandro Stefani , Hilkka Soininen , Johannes Schroder , Leslie M. Shaw , Anders Skinningsrud , Brith Skrogstad and Annette Spreer
  Background The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer‘s disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer‘s Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program. Methods The program is open for laboratories using commercially available kits for Aβ, T-tau, or P-tau. CSF samples (aliquots of pooled CSF) are sent for analysis several times a year from the Clinical Neurochemistry Laboratory at the Molndal campus of the University of Gothenburg, Sweden. Each round consists of three quality control samples. Results Forty laboratories participated. Twenty-six used INNOTEST enzyme-linked immunosorbent assay kits, 14 used Luminex xMAP with the INNO-BIA AlzBio3 kit (both measure Aβ-(1-42), P-tau(181P), and T-tau), and 5 used Meso Scale Discovery with the Aβ triplex (AβN-42, AβN-40, and AβN-38) or T-tau kits. The total coefficients of variation between the laboratories were 13% to 36%. Five laboratories analyzed the samples six times on different occasions. Within-laboratory precisions differed considerably between biomarkers within individual laboratories. Conclusions Measurements of CSF AD biomarkers show large between-laboratory variability, likely caused by factors related to analytical procedures and the analytical kits. Standardization of laboratory procedures and efforts by kit vendors to increase kit performance might lower variability, and will likely increase the usefulness of CSF AD biomarkers.
  Constantine G. Lyketsos , Maria C. Carrillo , J. Michael Ryan , Ara S. Khachaturian , Paula Trzepacz , Joan Amatniek , Jesse Cedarbaum , Robert Brashear and David S. Miller
  Neuropsychiatric symptoms (NPS) are core features of Alzheimer‘s disease and related dementias. Once thought to emerge primarily in people with late-stage disease, these symptoms are currently known to manifest commonly in very early disease and in prodromal phases, such as mild cognitive impairment. Despite decades of research, reliable treatments for dementia-associated NPS have not been found, and those that are in widespread use present notable risks for people using these medications. An Alzheimer‘s Association Research Roundtable was convened in the spring of 2010 to review what is known about NPS in Alzheimer‘s disease, to discuss classification and underlying neuropathogenesis and vulnerabilities, and to formulate recommendations for new approaches to tailored therapeutics.
  Bradley T. Hyman , Creighton H. Phelps , Thomas G. Beach , Eileen H. Bigio , Nigel J. Cairns , Maria C. Carrillo , Dennis W. Dickson , Charles Duyckaerts , Matthew P. Frosch , Eliezer Masliah , Suzanne S. Mirra , Peter T. Nelson , Julie A. Schneider , Julie A. Schneider , Bill Thies , John Q. Trojanowski , Harry V. Vinters and Thomas J. Montine
  A consensus panel from the United States and Europe was convened recently to update and revise the 1997 consensus guidelines for the neuropathologic evaluation of Alzheimer's disease (AD) and other diseases of brain that are common in the elderly. The new guidelines recognize the pre-clinical stage of AD, enhance the assessment of AD to include amyloid accumulation as well as neurofibrillary change and neuritic plaques, establish protocols for the neuropathologic assessment of Lewy body disease, vascular brain injury, hippocampal sclerosis, and TDP-43 inclusions, and recommend standard approaches for the workup of cases and their clinico-pathologic correlation.
  Kristine Yaffe , Michael Tocco , Ronald C. Petersen , Catherine Sigler , Leah C. Burns , Christel Cornelius , Ara S. Khachaturian , Michael C. Irizarry and Maria C. Carrillo
  Epidemiological studies increasingly inform Alzheimer‘s disease (AD) public health impact, prevention strategies, drug targets, therapeutic interventions, and clinical trial design. For this reason, the Alzheimer‘s Association Research Roundtable convened an international group of AD experts with experience in conducting both observational and clinical trials for a meeting on October 19 and 20, 2010, in Washington, DC, to discuss the role of epidemiologic studies in AD research and therapeutic advances. Topics included wellness markers and risk factors, with a focus on special populations such as those at elevated risk, super agers, and underserved populations. Discussions also highlighted lessons learned from observational studies of aging, cardiovascular disease, and other disease areas, as well as how new technologies have enabled the gathering of data relevant to drug development and clinical trial conduct.
  Maria C. Carrillo , Lisa J. Bain , Giovanni B. Frisoni and Michael W. Weiner
  The Alzheimer‘s Disease Neuroimaging Initiative (ADNI) was launched in 2003 to speed drug development by validating imaging and blood/cerebrospinal fluid biomarkers for Alzheimer‘s disease clinical treatment trials. ADNI is a naturalistic (nontreatment) multisite longitudinal study. A true public–private partnership, the first phase of ADNI (ADNI 1) set a new standard for data sharing without embargo. In addition, it has been extended to 2017 by additional funding (North American-ADNI Grand Opportunities and ADNI 2) as well as multiple projects around the world, collectively known as Worldwide ADNI (WW-ADNI). The goal of WW-ADNI is to harmonize projects and results across different geographical sites and to encourage and harmonize data management and availability to investigators around the world. WW-ADNI projects are currently underway in North America, Europe, Japan, Australia, Korea, Taiwan, and Argentina, with a nascent program in China and a possible future program in Brazil.
  Lorenzo M. Refolo , Heather Snyder , Charlene Liggins , Laurie Ryan , Nina Silverberg , Suzana Petanceska and Maria C. Carrillo
  Alzheimer‘s disease is recognized as a public health crisis worldwide. As public and private funding agencies around the world enhance and expand their support of Alzheimer‘s disease research, there is an urgent need to coordinate funding strategies and leverage resources to maximize the impact on public health and avoid duplication of effort and inefficiency. Such coordination requires a comprehensive assessment of the current landscape of Alzheimer‘s disease research in the United States and internationally. To this end, the National Institute on Aging at the National Institutes of Health and the Alzheimer‘s Association developed the Common Alzheimer‘s Disease Research Ontology (CADRO) as a dynamic portfolio analysis tool that can be used by funding agencies worldwide for strategic planning and coordination.
  Barry D. Greenberg , Maria C. Carrillo , J. Michael Ryan , Michael Gold , Kim Gallagher , Michael Grundman , Robert M. Berman , Timothy Ashwood and Eric R. Siemers
  Over the past 30 years, many drugs have been studied as possible treatments for Alzheimer‘s disease, but only four have demonstrated sufficient efficacy to be approved as treatments, of which three are in the same class. This lack of success has raised questions both in the pharmaceutical industry and academia about the future of Alzheimer‘s disease therapy. The high cost and low success rate of drug development across many disease areas can be attributed, in large part, to late-stage clinical failures (Schachter and Ramoni, Nat Rev Drug Discov 2007;6:107–8). Thus, identifying in phase II, or preferably phase I, drugs that are likely to fail would have a dramatic impact on the costs associated with developing new drugs. With this in mind, the Alzheimer‘s Association convened a Research Roundtable on June 23 and 24, 2011, in Washington, DC, bringing together scientists from academia, industry, and government regulatory agencies to discuss strategies for improving the probability of phase II trial results predicting success when considering the go/no-go decision-making process leading to the initiation of phase III.
  Maria C. Carrillo , H. Robert Brashear , Veronika Logovinsky , J. Michael Ryan , Howard H. Feldman , Eric R. Siemers , Susan Abushakra , Dean M. Hartley , Ronald C. Petersen , Ara S. Khachaturian and Reisa A. Sperling
  Current research including the basic biology of Alzheimer's disease (AD) provides a foundation to explore whether our current state of knowledge is sufficient to initiate prevention studies and allow us to believe prevention of AD is possible. Current research and recently revised criteria for the diagnosis of AD by the National Institutes on Aging and the Alzheimer's Association suggest a continuum of disease from preclinical asymptomatic to symptomatic Alzheimer's dementia. In light of these revised criteria, the possibility of secondary prevention and even primary prevention is under discussion. The Alzheimer's Association Research Roundtable convened a meeting to discuss the rationale and feasibility of conducting secondary prevention trials in AD.
  Maria C. Carrillo , Kaj Blennow , Holly Soares , Piotr Lewczuk , Niklas Mattsson , Pankaj Oberoi , Robert Umek , Manu Vandijck , Salvatore Salamone , Tobias Bittner , Leslie M. Shaw , Diane Stephenson , Lisa Bain and Henrik Zetterberg
  Recognizing that international collaboration is critical for the acceleration of biomarker standardization efforts and the efficient development of improved diagnosis and therapy, the Alzheimer's Association created the Global Biomarkers Standardization Consortium (GBSC) in 2010. The consortium brings together representatives of academic centers, industry, and the regulatory community with the common goal of developing internationally accepted common reference standards and reference methods for the assessment of cerebrospinal fluid (CSF) amyloid β42 (Aβ42) and tau biomarkers. Such standards are essential to ensure that analytical measurements are reproducible and consistent across multiple laboratories and across multiple kit manufacturers. Analytical harmonization for CSF Aβ42 and tau will help reduce confusion in the AD community regarding the absolute values associated with the clinical interpretation of CSF biomarker results and enable worldwide comparison of CSF biomarker results across AD clinical studies.
  Maria C. Carrillo , Christopher C. Rowe , Cassandra Szoeke , Colin L. Masters , David Ames , Tim O’Meara , S. Lance Macaulay , Andrew Milner , Kathryn A. Ellis , Paul Maruff , Stephanie R. Rainey- Smith , Ralph N. Martins , Lisa J. Bain and Richard J. Head
  Alzheimer's disease (AD) is an epidemic facing the entire world. Increased knowledge gained during the past 25 years indicates that AD falls along a clinical and neuropathological spectrum represented as a continuum that extends from preclinical disease in which there are no symptoms, through early symptomatic phases, and finally to AD dementia. The Alzheimer's research community recognizes that imaging, body fluids, and cognitive biomarkers contribute to enhanced diagnostic confidence for AD. There has also been emerging consensus regarding the use of AD biomarkers in clinical trials. The use of biomarkers in clinical trials and practice is hampered by the lack of standardization. In response to the emerging need for standardization, an international meeting of AD researchers was held in Melbourne, Australia, in March 2012 to bring together key researchers, clinicians, industry, and regulatory stakeholders with the aim of generating consensus on standardization and validation of cognitive, imaging, and fluid biomarkers, as well as lifestyle parameters used in research centers worldwide.
  Niklas Mattsson , Ulf Andreasson , Staffan Persson , Maria C. Carrillo , Steven Collins , Sonia Chalbot , Neal Cutler , Diane Dufour- Rainfray , Anne M. Fagan , Niels H.H. Heegaard , Ging-Yuek Robin Hsiung , Bradley Hyman , Khalid Iqbal , D. Richard Lachno , Alberto Lleo , Piotr Lewczuk , Jose L. Molinuevo , Piero Parchi , Axel Regeniter , Robert Rissman , Hanna Rosenmann , Giuseppe Sancesario , Johannes Schroder , Leslie M. Shaw , Charlotte E. Teunissen , John Q. Trojanowski , Hugo Vanderstichele , Manu Vandijck , Marcel M. Verbeek , Henrik Zetterberg , Kaj Blennow and Stephan A. Kaser
  Background The cerebrospinal fluid (CSF) biomarkers amyloid beta 1–42, total tau, and phosphorylated tau are used increasingly for Alzheimer's disease (AD) research and patient management. However, there are large variations in biomarker measurements among and within laboratories. Methods Data from the first nine rounds of the Alzheimer's Association quality control program was used to define the extent and sources of analytical variability. In each round, three CSF samples prepared at the Clinical Neurochemistry Laboratory (Molndal, Sweden) were analyzed by single-analyte enzyme-linked immunosorbent assay (ELISA), a multiplexing xMAP assay, or an immunoassay with electrochemoluminescence detection. Results A total of 84 laboratories participated. Coefficients of variation (CVs) between laboratories were around 20% to 30%; within-run CVs, less than 5% to 10%; and longitudinal within-laboratory CVs, 5% to 19%. Interestingly, longitudinal within-laboratory CV differed between biomarkers at individual laboratories, suggesting that a component of it was assay dependent. Variability between kit lots and between laboratories both had a major influence on amyloid beta 1–42 measurements, but for total tau and phosphorylated tau, between-kit lot effects were much less than between-laboratory effects. Despite the measurement variability, the between-laboratory consistency in classification of samples (using prehoc-derived cutoffs for AD) was high (>90% in 15 of 18 samples for ELISA and in 12 of 18 samples for xMAP). Conclusions The overall variability remains too high to allow assignment of universal biomarker cutoff values for a specific intended use. Each laboratory must ensure longitudinal stability in its measurements and use internally qualified cutoff levels. Further standardization of laboratory procedures and improvement of kit performance will likely increase the usefulness of CSF AD biomarkers for researchers and clinicians.
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