Current and future treatments for Alzheimer's disease.
TLDR
Current symptomatic treatments and new potential disease-modifying therapies for AD that are currently being studied in phase I–III trials are discussed.Abstract:
Alzheimer’s dementia (AD) is increasingly being recognized as one of the most important medical and social problems in older people in industrialized and non-industrialized nations. To date, only symptomatic treatments exist for this disease, all trying to counterbalance the neurotransmitter disturbance. Three cholinesterase inhibitors (CIs) are currently available and have been approved for the treatment of mild to moderate AD. A further therapeutic option available for moderate to severe AD is memantine, an N-methyl-D-aspartate receptor noncompetitive antagonist. Treatments capable of stopping or at least effectively modifying the course of AD, referred to as ‘disease-modifying’ drugs, are still under extensive research. To block the progression of the disease they have to interfere with the pathogenic steps responsible for the clinical symptoms, including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation, inflammation, oxidative damage, iron deregulati...read more
Citations
More filters
Journal ArticleDOI
Binding of ACE-inhibitors to in vitro and patient-derived amyloid-β fibril models.
Manikanthan Bhavaraju,Malachi Phillips,Deborah Bowman,Juan Manuel Aceves-Hernández,Ulrich H. E. Hansmann +4 more
TL;DR: It is found that ACE inhibitors have a lower binding affinity to the patient-derived fibrils than to in vitro generated ones, which raises doubts on the hypothesis that these drugs inhibit fibril formation in Alzheimer patients by interacting directly with the amyloids.
Journal ArticleDOI
Preventing Alzheimer's disease within reach by 2025: Targeted-risk-AD-prevention (TRAP) strategy
TL;DR: In this paper, a combination of text-mining and natural language processing strategies was used to identify AD risk factors, therapeutics that can target risk factor pathways, and studies supporting therapeutics in the PubMed database.
Dissertation
Selection of RNA aptamers and their recognition of amyloid assemblies
TL;DR: The results demonstrate an inherent affinity for amyloid by RNA molecules, making it highly challenging to select aptamers able to distinguish between different cross-β assemblies, however, the seemingly universal amyloids-binding propensity demonstrated by RNA could allow development of genericAmyloid detection tools, more effective than current methods.
Journal ArticleDOI
Synthesis and Bioinformatic Characterization of New Schiff Bases with Possible Applicability in Brain Disorders.
Speranta Avram,Ana Maria Udrea,Diana Camelia Nuta,Carmen Limban,Adrian Cosmin Balea,Miron Teodor Caproiu,Florea Dumitrascu,Catalin Buiu,Alexandra Teodora Bordei +8 more
TL;DR: In this paper, a bioinformatics and pathology study of new Schiff bases, (EZ)-N′-benzylidene-(2RS)-2-(6-chloro-9H-carbazol-2-yl)propanehydrazide derivatives, and aims to evaluate the drug-like, pharmacokinetic, pharmacodynamic and pharmacogenomic properties.
Journal ArticleDOI
High ligand efficiency quinazoline compounds as novel A2A adenosine receptor antagonists.
Raphaël Bolteau,Romain Duroux,Amélie Laversin,Brandon Vreulz,Anna Shiriaeva,Benjamin Stauch,Gye Won Han,Vadim Cherezov,Nicolas Renault,Amélie Barczyk,Séverine Ravez,Mathilde Coevoet,Patricia Melnyk,Maxime Liberelle,Saïd Yous +14 more
TL;DR: In this paper , a series of 2-aminoquinazoline derivatives were identified as promising A2AAR antagonists and one compound showed a high affinity towards A 2AAR (21a, Ki = 20 nM), confirming one of their predicted docking poses and opening up possibilities for further optimization to derive selective ligands for specific adenosine receptor subtypes.
References
More filters
Journal ArticleDOI
Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease
Reisa A. Sperling,Paul S. Aisen,Laurel A. Beckett,David A. Bennett,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,Kristine Yaffe,Maria C. Carrillo,Bill Thies,Marcelle Morrison-Bogorad,Molly V. Wagster,Creighton H. Phelps +20 more
TL;DR: A conceptual framework and operational research criteria are proposed, based on the prevailing scientific evidence to date, to test and refine these models with longitudinal clinical research studies and it is hoped that these recommendations will provide a common rubric to advance the study of preclinical AD.
Journal ArticleDOI
The Cholinergic Hypothesis of Geriatric Memory Dysfunction
Raymond T. Bartus,Raymond T. Bartus,Reginald L. Dean,Bernard Beer,Bernard Beer,Arnold S. Lippa,Arnold S. Lippa +6 more
TL;DR: Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed and an attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature.
Journal ArticleDOI
Global prevalence of dementia: a Delphi consensus study
Cleusa P. Ferri,Martin Prince,Carol Brayne,Henry Brodaty,Laura Fratiglioni,Mary Ganguli,Kathleen S. Hall,Kazuo Hasegawa,Hugh C. Hendrie,Yueqin Huang,Anthony F. Jorm,Colin Mathers,Paulo Rossi Menezes,Elizabeth Rimmer,Marcia Scazufca +14 more
TL;DR: Detailed estimates of dementia prevalence for each world region are believed to constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources.
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
Statins and the risk of dementia.
Hershel Jick,Gwen L. Zornberg,Gwen L. Zornberg,Susan S. Jick,Sudha Seshadri,David A. Drachman +5 more
TL;DR: Individuals of 50 years and older who were prescribed statins had a substantially lowered risk of developing dementia, independent of the presence or absence of untreated hyperlipidaemia, or exposure to nonstatin LLAs.
Related Papers (5)
The Amyloid Hypothesis of Alzheimer's Disease: Progress and Problems on the Road to Therapeutics
John Hardy,Dennis J. Selkoe +1 more
Neuroinflammation in Alzheimer's disease
Michael T. Heneka,Monica J. Carson,Joseph El Khoury,Gary E. Landreth,Frederic Brosseron,Douglas L. Feinstein,Andreas H. Jacobs,Tony Wyss-Coray,Tony Wyss-Coray,Javier Vitorica,Richard M. Ransohoff,Karl Herrup,Sally A. Frautschy,Bente Finsen,Guy C. Brown,Alexei Verkhratsky,Alexei Verkhratsky,Alexei Verkhratsky,Koji Yamanaka,Jari Koistinaho,Eicke Latz,Eicke Latz,Annett Halle,Gabor C. Petzold,Terrence Town,Dave Morgan,Mari L. Shinohara,V. Hugh Perry,Clive Holmes,Clive Holmes,Nicolas G. Bazan,David J. Brooks,Stéphane Hunot,Bertrand Joseph,Nikolaus Deigendesch,Olga Garaschuk,Erik Boddeke,Charles A. Dinarello,John C.S. Breitner,Greg M. Cole,Douglas T. Golenbock,Markus P. Kummer +41 more