Drug treatments in Alzheimer's disease.
TLDR
Techniques providing earlier diagnosis, such as cerebrospinal fluid biomarkers and amyloid positron emission tomography neuroimaging, are key to testing this theory in clinical trials and results from trials of agents such as aducanumab are encouraging but must also be interpreted with caution.Abstract:
Despite the significant public health issue that it poses, only five medical treatments have been approved for Alzheimer's disease (AD) and these act to control symptoms rather than alter the course of the disease. Studies of potential disease-modifying therapy have generally been undertaken in patients with clinically detectable disease, yet evidence suggests that the pathological changes associated with AD begin several years before this. It is possible that pharmacological therapy may be beneficial in this pre-clinical stage before the neurodegenerative process is established. Techniques providing earlier diagnosis, such as cerebrospinal fluid biomarkers and amyloid positron emission tomography neuroimaging, are key to testing this theory in clinical trials. Recent results from trials of agents such as aducanumab are encouraging but must also be interpreted with caution. Such medicines could potentially delay the onset of dementia and would therefore markedly reduce its prevalence. However, we currently remain a good distance away from clinically available disease-modifying therapy.read more
Citations
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Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade
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Michiel Van Bulck,Ana Sierra-Magro,Jesus Alarcon-Gil,Ana Perez-Castillo,José A. Morales-García,José A. Morales-García +5 more
TL;DR: The most common features of major neurodegenerative disorders, their causes and consequences, and the proposed novel therapeutic approaches are summarized.
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Blood-brain barrier-penetrating siRNA nanomedicine for Alzheimer's disease therapy.
Yutong Zhou,Feiyan Zhu,Yang Liu,Meng Zheng,Yibin Wang,Dongya Zhang,Yasutaka Anraku,Yan Zou,Yan Zou,Jia Li,Haigang Wu,Xiaobin Pang,Wei Tao,Olga Shimoni,Ashley I. Bush,Xue Xue,Bingyang Shi,Bingyang Shi +17 more
TL;DR: Glycosylated “triple-interaction” stabilized siRNA nanomedicine ameliorated AD neuropathology by targeting BACE1 and restored the deterioration of cognitive capacity in AD mice without notable side effects, which supports the utility of RNA interference therapy in neurodegenerative diseases.
References
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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
Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
Elizabeth H. Corder,Ann M. Saunders,Warren J. Strittmatter,Donald E. Schmechel,P. C. Gaskell,Gary W. Small,A. D. Roses,Jonathan L. Haines,Margaret A. Pericak-Vance +8 more
TL;DR: The APOE-epsilon 4 allele is associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD) in 42 families with late onset AD.
Journal ArticleDOI
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
TL;DR: Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction.
Journal ArticleDOI
Effects of Age, Sex, and Ethnicity on the Association Between Apolipoprotein E Genotype and Alzheimer Disease: A Meta-analysis
Lindsay A. Farrer,L. Adrienne Cupples,Jonathan L. Haines,Bradley T. Hyman,Walter A. Kukull,Richard Mayeux,Richard H. Myers,Margaret A. Pericak-Vance,Neil Risch,Cornelia M. van Duijn +9 more
TL;DR: The APOE∈4 allele represents a major risk factor for AD in all ethnic groups studied, across all ages between 40 and 90 years, and in both men and women.
Journal ArticleDOI
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
TL;DR: The A β-dependent and Aβ-independent mechanisms that link Apo-E4 status with AD risk are discussed, and how to design effective strategies for AD therapy by targeting ApO-E is considered.
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