Journal ArticleDOI
Cerebrospinal fluid and plasma biomarkers in Alzheimer disease.
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TLDR
The rationales behind and the diagnostic performances of the core cerebrospinal fluid biomarkers for AD, namely total tau, phosphorylated tau and the 42 amino acid form of amyloid-β are presented.Abstract:
Intense multidisciplinary research has provided detailed knowledge of the molecular pathogenesis of Alzheimer disease (AD). This knowledge has been translated into new therapeutic strategies with putative disease-modifying effects. Several of the most promising approaches, such as amyloid-beta immunotherapy and secretase inhibition, are now being tested in clinical trials. Disease-modifying treatments might be at their most effective when initiated very early in the course of AD, before amyloid plaques and neurodegeneration become too widespread. Thus, biomarkers are needed that can detect AD in the predementia phase or, ideally, in presymptomatic individuals. In this Review, we present the rationales behind and the diagnostic performances of the core cerebrospinal fluid (CSF) biomarkers for AD, namely total tau, phosphorylated tau and the 42 amino acid form of amyloid-beta. These biomarkers reflect AD pathology, and are candidate markers for predicting future cognitive decline in healthy individuals and the progression to dementia in patients who are cognitively impaired. We also discuss emerging plasma and CSF biomarkers, and explore new proteomics-based strategies for identifying additional CSF markers. Furthermore, we outline the roles of CSF biomarkers in drug discovery and clinical trials, and provide perspectives on AD biomarker discovery and the validation of such markers for use in the clinic.read more
Citations
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Journal ArticleDOI
NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease
Clifford R. Jack,David A. Bennett,Kaj Blennow,Maria C. Carrillo,Billy Dunn,Samantha Budd Haeberlein,David M. Holtzman,William J. Jagust,Frank Jessen,Jason Karlawish,Enchi Liu,José Luis Molinuevo,Thomas J. Montine,Creighton H. Phelps,Katherine P. Rankin,Christopher C. Rowe,Philip Scheltens,Eric Siemers,Heather M. Snyder,Reisa A. Sperling,Cerise L Elliott,Eliezer Masliah,Laurie M. Ryan,Nina Silverberg +23 more
TL;DR: This research framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms and envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD.
Journal ArticleDOI
Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria
Bruno Dubois,Bruno Dubois,Howard Feldman,Claudia Jacova,Harald Hampel,Harald Hampel,José Luis Molinuevo,Kaj Blennow,Steven T. DeKosky,Serge Gauthier,Dennis J. Selkoe,Randall J. Bateman,Stefano F. Cappa,Sebastian J. Crutch,Sebastiaan Engelborghs,Giovanni B. Frisoni,Nick C. Fox,Douglas Galasko,Marie-Odile Habert,Gregory A. Jicha,Agneta Nordberg,Florence Pasquier,Gil D. Rabinovici,Philippe Robert,Christopher C. Rowe,Stephen Salloway,Marie Sarazin,Stéphane Epelbaum,Stéphane Epelbaum,Leonardo Cruz de Souza,Leonardo Cruz de Souza,Leonardo Cruz de Souza,Bruno Vellas,Pieter Jelle Visser,Lon S. Schneider,Yaakov Stern,Philip Scheltens,Jeffrey L. Cummings +37 more
TL;DR: It is proposed 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.
Journal ArticleDOI
Revising the definition of Alzheimer's disease: a new lexicon.
Bruno Dubois,Howard Feldman,Howard Feldman,Howard Feldman,Claudia Jacova,Jeffrey L. Cummings,Steven T. DeKosky,Pascale Barberger-Gateau,André Delacourte,Giovanni B. Frisoni,Nick C. Fox,Douglas Galasko,Serge Gauthier,Harald Hampel,Gregory A. Jicha,Kenichi Meguro,John T. O'Brien,Florence Pasquier,Philippe Robert,Martin N. Rossor,Steven Salloway,Marie Sarazin,Leonardo Cruz de Souza,Yaakov Stern,Pieter Jelle Visser,Pieter Jelle Visser,Philip Scheltens +26 more
TL;DR: This paper aims to advance the scientific discussion by providing broader diagnostic coverage of the AD clinical spectrum and by proposing a common lexicon as a point of reference for the clinical and research communities.
Journal ArticleDOI
CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis
Bob Olsson,Ronald Lautner,Ulf Andreasson,Annika Öhrfelt,Erik Portelius,Maria Bjerke,Maria Bjerke,Mikko Hölttä,Christoffer Rosén,Caroline Olsson,Gabrielle Strobel,Elizabeth Wu,Kelly Dakin,Max Petzold,Max Petzold,Kaj Blennow,Henrik Zetterberg,Henrik Zetterberg +17 more
TL;DR: The core CSF biomarkers of neurodegeneration (T-tau, P-tAU, and Aβ42), CSF NFL, and plasma T-t Tau were strongly associated with Alzheimer's disease and the core biomarkers were strong associated with mild cognitive impairment due to Alzheimer's Disease.
References
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Journal ArticleDOI
Clinical diagnosis of Alzheimer's disease : report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
Guy M. McKhann,David A. Drachman,Marshall F. Folstein,Robert Katzman,Donald L. Price,Emanuel M. Stadlan +5 more
TL;DR: The criteria proposed are intended to serve as a guide for the diagnosis of probable, possible, and definite Alzheimer's disease; these criteria will be revised as more definitive information becomes available.
Journal ArticleDOI
The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
John Hardy,Dennis J. Selkoe +1 more
TL;DR: It has been more than 10 years since it was first proposed that the neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid β-peptide in plaques in brain tissue and the rest of the disease process is proposed to result from an imbalance between Aβ production and Aβ clearance.
Journal ArticleDOI
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Jie Kang,H. G. Lemaire,A. Unterbeck,J. M. Salbaum,Colin L. Masters,K.-H. Grzeschik,Gerd Multhaup,Konrad Beyreuther,Benno Müller-Hill +8 more
TL;DR: An apparently full-length complementary DNA clone coding for the A4 polypeptide is isolated and sequenced and suggests that the cerebral amyloid deposited in Alzheimer's disease and aged Down's syndrome is caused by aberrant catabolism of a cell-surface receptor.
Journal ArticleDOI
Amyloid plaque core protein in Alzheimer disease and Down syndrome
Colin L. Masters,Gail Simms,Nicola A. Weinman,Gerd Multhaup,Brian L. McDonald,Konrad Beyreuther +5 more
TL;DR: The shared 4-kDa subunit indicates a common origin for the amyloids of the plaque core and of the congophilic angiopathy of Alzheimer disease and Down syndrome.
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