Journal ArticleDOI
A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease.
Stephen Salloway,Martin R. Farlow,Eric McDade,David B. Clifford,Guoqiao Wang,Jorge J. Llibre-Guerra,Janice M. Hitchcock,Susan Mills,Anna Santacruz,Andrew J. Aschenbrenner,Jason Hassenstab,Tammie L.S. Benzinger,Brian A. Gordon,Anne M. Fagan,Kelley Coalier,Carlos Cruchaga,Alison Goate,Richard J. Perrin,Chengjie Xiong,Yan Li,John C. Morris,B. Joy Snider,Catherine J. Mummery,G. Mustafa Surti,Didier Hannequin,David Wallon,Sarah B. Berman,James J. Lah,Ivonne Z. Jimenez-Velazquez,Erik D. Roberson,Christopher H. van Dyck,Lawrence S. Honig,Raquel Sánchez-Valle,William S. Brooks,Serge Gauthier,Douglas Galasko,Colin L. Masters,Jared R. Brosch,Ging-Yuek Robin Hsiung,Suman Jayadev,Maïté Formaglio,Mario Masellis,Roger Clarnette,J. Pariente,Bruno Dubois,Florence Pasquier,Clifford R. Jack,Robert A. Koeppe,Peter J. Snyder,Paul S. Aisen,Ronald G. Thomas,Scott M. Berry,Barbara A. Wendelberger,Scott W. Andersen,Karen C. Holdridge,Mark A. Mintun,Roy Yaari,John R. Sims,Monika Baudler,Paul Delmar,Rachelle S. Doody,Paulo Fontoura,Caroline Giacobino,Geoffrey A. Kerchner,Randall J. Bateman +64 more
TLDR
A randomized, placebo-controlled, multi-arm trial of gantenerumab or solanezumab in participants with DIAD across asymptomatic and symptomatic disease stages was conducted in this paper.Abstract:
Dominantly inherited Alzheimer's disease (DIAD) causes predictable biological changes decades before the onset of clinical symptoms, enabling testing of interventions in the asymptomatic and symptomatic stages to delay or slow disease progression. We conducted a randomized, placebo-controlled, multi-arm trial of gantenerumab or solanezumab in participants with DIAD across asymptomatic and symptomatic disease stages. Mutation carriers were assigned 3:1 to either drug or placebo and received treatment for 4-7 years. The primary outcome was a cognitive end point; secondary outcomes included clinical, cognitive, imaging and fluid biomarker measures. Fifty-two participants carrying a mutation were assigned to receive gantenerumab, 52 solanezumab and 40 placebo. Both drugs engaged their Aβ targets but neither demonstrated a beneficial effect on cognitive measures compared to controls. The solanezumab-treated group showed a greater cognitive decline on some measures and did not show benefits on downstream biomarkers. Gantenerumab significantly reduced amyloid plaques, cerebrospinal fluid total tau, and phospho-tau181 and attenuated increases of neurofilament light chain. Amyloid-related imaging abnormalities edema was observed in 19.2% (3 out of 11 were mildly symptomatic) of the gantenerumab group, 2.5% of the placebo group and 0% of the solanezumab group. Gantenerumab and solanezumab did not slow cognitive decline in symptomatic DIAD. The asymptomatic groups showed no cognitive decline; symptomatic participants had declined before reaching the target doses.read more
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Antibodies to watch in 2022
TL;DR: The data show that, with antibodies for COVID-19 excluded, the late-stage commercial clinical pipeline of antibody therapeutics grew by over 30% in the past year, and marketing applications for at least 22 products may occur by the end of 2022.
Journal ArticleDOI
The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics
Eric Karran,Bart De Strooper +1 more
TL;DR: In this article , the temporal interplay between the two pathognomonic protein aggregates in AD and their relationship to cognitive impairment was investigated. And the authors concluded that the speed of amyloid removal from the brain by a potential therapy will be important in demonstrating clinical benefit in the context of clinical trial.
Journal ArticleDOI
The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics
Eric Karran,Bart De Strooper +1 more
TL;DR: In this article , the temporal interplay between the two pathognomonic protein aggregates in AD and their relationship to cognitive impairment was investigated. And the authors concluded that the speed of amyloid removal from the brain by a potential therapy will be important in demonstrating clinical benefit in the context of clinical trial.
Journal ArticleDOI
The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease
Oskar Hansson,Rebecca M. Edelmayer,Adam L. Boxer,Maria C. Carrillo,Michelle M. Mielke,Gil D. Rabinovici,Stephen Salloway,Reisa A. Sperling,Henrik Zetterberg,Charlotte E. Teunissen +9 more
TL;DR: Additional data are needed before use of BBMs as stand-alone diagnostic AD markers, or before considering use in primary care, and it is recommended to cautiously start using BBMs in specialized memory clinics as part of the diagnostic work-up of patients with cognitive symptoms.
Journal ArticleDOI
The Alzheimer's Association appropriate use recommendations for blood biomarkers in Alzheimer's disease
Oskar Hansson,Rebecca M. Edelmayer,Adam L. Boxer,Maria C. Carrillo,Michelle M. Mielke,Gil D. Rabinovici,Stephen Salloway,Reisa A. Sperling,Henrik Zetterberg,Charlotte E. Teunissen +9 more
TL;DR: In this paper, the authors discuss further research needed to be performed before widespread use of blood-based markers (BBMs) for diagnostic and prognostic work-up of Alzheimer's disease.
References
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“Mini-mental state”: A practical method for grading the cognitive state of patients for the clinician
Marshal F. Folstein,Marshal F. Folstein,Susan E B Folstein,Susan E B Folstein,Paul R. McHugh,Paul R. McHugh +5 more
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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
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Automatically Parcellating the Human Cerebral Cortex
Bruce Fischl,Andre van der Kouwe,Christophe Destrieux,Eric Halgren,Florent Ségonne,David H. Salat,Evelina Busa,Larry J. Seidman,Jill M. Goldstein,David N. Kennedy,Verne S. Caviness,Nikos Makris,Bruce R. Rosen,Anders M. Dale +13 more
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Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease
Randall J. Bateman,Chengjie Xiong,Tammie L.S. Benzinger,Anne M. Fagan,Alison Goate,Nick C. Fox,Daniel S. Marcus,Nigel J. Cairns,Xianyun Xie,Tyler Blazey,David M. Holtzman,Anna Santacruz,Virginia Buckles,Angela Oliver,Krista L. Moulder,Paul S. Aisen,Bernardino Ghetti,William E. Klunk,Eric McDade,Ralph N. Martins,Colin L. Masters,Richard Mayeux,John M. Ringman,Martin N. Rossor,Peter R. Schofield,Reisa A. Sperling,Stephen Salloway,John C. Morris +27 more
TL;DR: In this paper, a longitudinal study of 128 patients with Alzheimer's disease was conducted, where the authors used the participant's age at baseline assessment and the parent's age to calculate the estimated years from expected symptom onset (age of the participant minus parent's ages at symptom onset).
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