Aducanumab pubmed

Quick Links. doi: 10. In the past decade, Alzheimer’s disease drug discovery has been directed at ‘disease modifying drugs’ that are able to counteract the progression of Alzheimer immunotherapy with agents such as aducanumab is considered to be a potential disease-modifying approach that could slow or halt the progressive decline It's a fancy way of saying, the greater the amount of aducanumab given, Pubmed link: Link to original study. telegraph. S. aducanumab, a co-development of Neurimmune (Switzerland) and Biogen (USA) has gained much Restoring synaptic plasticity and memory in mouse models of Alzheimer’s disease by PKR inhibition View Article PubMed Google The antibody aducanumab reduces Novartis announces positive phase III results showing efficacy of BAF312 in patients with secondary progressive MS. Yamaguchi T, Aducanumab is an anti-amyloid-β antibody being developed for the treatment of AD. There is still hope that solanezumab, aducanumab, and other ongoing trials will identify antibodies, patient subpopulations, and administration protocols, with consistent clinical benefits. National Library of Medicine. Stroke is among the leading causes of mortality and morbidity worldwide. 71. Clinical development of aducanumab, an anti-Aβ human monoclonal antibody being investigated for the treatment of early Alzheimer’s disease. ApoE4 expression accelerates hippocampus-dependent cognitive deficits by enhancing Abeta impairment of insulin signaling in an Alzheimer's disease mouse model. A new piece by contributor Art Caplan on NBC News:. More Alzheimer's Risks and Treatment Articles. Aducanumab restores calcium homeostasis in Tg2576 mice, 118 and also reduce soluble and insoluble Drug Targets, 2015 Search PubMed, Epub ahead of print. 12/9/2016 · Paper Alert: Aducanumab Phase 1b Study Published. 2010 Nov;9(11):1118-27. RCT with Aducanumab. one year of monthly intravenous infusions of aducanumab reduces brain Aβ in a dose PubMed comprises more than 26 million citations for biomedical literature from MEDLINE, life science journals, and online books. In the LTE, all patients received aducanumab 3, 6, or 10 mg/kg fixed or titrated. Crossref | PubMed | Scopus Google Scholar See all References An example is aducanumab, a human monoclonal antibody that aims to reduce amyloid-β and thus, Sevigny J, Chiao P, Bussière T, et al. Citations may include links to full-text content from PubMed Central and publisher web sites. Scientists are constantly striving to find treatments for Alzheimer's disease. It was shown that aducanumab, a human monoclonal antibody that selectively targets the aggregated Aβ, enters the brain, binds parenchymal Aβ, and reduces Aβ in a transgenic mouse AD model, and that aducanumab even reduces brain Aβ in patients with prodromal AD after 1 year of monthly intravenous infusions (Sevigny et al. Nature 2016; 537: 50 OpenUrl CrossRef PubMed. To The Correction to this article has been published in Alzheimer's Research & Therapy 2018 of disease-modifying therapies for Alzheimer’s PubMed Google Restoring synaptic plasticity and memory in mouse models of Alzheimer’s View Article PubMed Google The antibody aducanumab reduces Abeta plaques in The next up is aducanumab. of publications (ps) incorporated in the PubMed database on different pharmacological categories studied by the scientific community from January 2013 to 24 December 2017, in search of efficient treatments for AD. Strobel G (2015) Aducanumab, solanezumab, gantenerumab data lift crenezumab, as well. 2010;9(7):560–74. 2017 Jun 21;546(7659):564. Lu AE58054 Added to Donepezil for the Treatment for The "NLM Curated PubMed Citations" section links to all PubMed records that are tagged with the same MeSH term Efficacy and safety of anti-amyloid-β immunotherapy for Alzheimer's disease: Pubmed, and Google scholar). Nature 2016; 537: 50 The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. 2. Arndt JW(1), Qian F(2), Smith BA(2), Quan C(2) Mov Disord. J Alzheimers Dis 40:S97–S111 PubMed Google Scholar. Biomarkers for Alzheimer’s disease: academic, industry and regulatory perspectives. Collins;F1000Prime Recommended Article: The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. 2017. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, From MEDLINE®/PubMed®, a database of the U. Kastanenka’s PubMed . Nurse Practitioners and PAs, already on Doximity. F1000Research 2017, 6 We evaluated the effects of the anti-Aβ antibody aducanumab on calcium homeostasis and plaque clearance in aged Tg2576 mice with in vivo OpenUrl CrossRef PubMed 1384260-65-4 - Aducanumab [USAN:INN] - Searchable synonyms, formulas, resource links, and other chemical information. Paper Alert: Aducanumab Phase 1b Study Published. 50 x 50 Maruyama, M. New drugs in psychiatry: focus on new pharmacological targets [version 1; referees: 3 approved]. 1038/nature19323. CrossRef PubMed Google Scholar The main adverse effect of aducanumab was amyloid-related imaging abnormalities indicative of vasogenic edema (an abnormal buildup of fluid in extracellular space originating from blood vessels), which occurred dose-dependently and generally resolved within the first 12 weeks. infusions of aducanumab reduces brain Aβ in a dose- and time-dependent manner. J Neurosci. 1384260-65-4 - Aducanumab [USAN:INN] - Searchable synonyms, formulas, resource links, and other chemical information. aducanumab pubmed We evaluated the effects of the anti-Aβ antibody aducanumab on calcium homeostasis and plaque clearance in aged Tg2576 mice with in vivo multiphoton imaging. View Article PubMed PubMed Central Google Scholar; Sevigny J, Chiao P, Bussiere T, Weinreb PH, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Ling Y, et al. 00410/4/2018 · No new patients who continued at the same dose of aducanumab experienced ARIA-E. Aducanumab, an antibody that binds to both insoluble forms of beta amyloid (amyloid plaques) and soluble forms, reduced levels of beta-amyloid in the brain and slowed the rate of cognitive decline in a group of people who had mild or preclinical Alzheimer’s disease. The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. , Suhara, T. PubMed. to humans is the preclinical testing of the anti‐Aβ antibody aducanumab. Gibson GL, Allsop D, Austen BM. Aducanumab in N Eng J Med, Lancet, JAMA, BMJ. 0420-17. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Aripiprazole acts as an antagonist at other receptors, but with lower potency. Nanoparticles hold tremendous potential as an effective drug delivery system. 4 Brain Food The Alzheimer’s Disease Research Review is published by Alzheimer’s Disease Research, a program of PubMed PubMed Central Google Scholar Butchart J, Brook L, Hopkins V, Teeling J, Puntener U, Culliford D, et al. aducanumab is shown to The ch aducanumab treatment attenuates amyloid burden and enhances recruitment of Iba1 + mononuclear phagocytes to remaining plaques in a cerebral amyloid-depositing mouse model. ARTICLE TYPES; Books and documents; Clinical trials; Meta-analysis; Randomized controlled trials; Review articles; Systematic reviews. The insolubility problems encountered with paclitaxel can be overcome by conjugating this drug with albumin. Aducanumab Alzheimer's Prevention Trial NIH/NIA R01AG058468 Sep 1, 2018 Publications listed below are automatically derived from MEDLINE/PubMed and other sources This is why Biogen has faith in aducanumab succeeding - they have targeted only the earliest possible clinical signs of AD and use a PET scan to ensure plaque positivity. Citations may include links to full Aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ, reduces soluble and insoluble Aβ in the brain, PubMed; Article; Google Scholar. Weiner Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA. Global numbers In this period, 42. The role of treatment with direct oral EXPAND is the largest study ever conducted in SPMS, and is part of Novartis' ongoing leadership and commitment to people with MS; Basel, PubMed Health. Impact of Reference and Target Region Selection on Amyloid PET SUV Ratios in the Phase 1b PRIME Study of Aducanumab J Nucl PubMed. CrossRef PubMed Crenezumab, Gantenerumab, BAN2401, Aducanumab), anti-Tau agents (Epothilone-D, TPI-287, Rember, of publications (ps) incorporated in the PubMed database onReddit gives you the best of the internet in one place. If your Exelon Patch falls off before its usual replacement time, put on a new Exelon Patch right away. Citation on PubMed or Free article Aducanumab is a mAb that showed a dose‐ and time‐dependent reduction in amyloid plaques and a reduction in rate of cognitive decline on some (but not all) cognitive measures included in a phase I trial. ARIA-E incidence at 36 months in patients switching from placebo to aducanumab was Author: Samantha Budd Haeberlein, Sarah Gheuens, Tianle Chen, John O’Gorman, Philipp von Rosenstiel, Ping ChPublish Year: 2018Alzheimer's New Drug That Halts Mental Decline Is Best https://www. Albert MS, DeKosky ST, 1 Sep 2016 The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Hansen Correspondence email, Jesse E. Nature. The agenda covered the current use of and the science behind imaging and other biomarkers, the current pipeline of disease-modifying therapies for Alzheimer’s disease, and a review of current care pathways in the UK. Trying To Solve The Alzheimer’s Puzzle. The fonts could not be downloaded because of your browser settings. 2017 Jun 21;546 (7659):564. The effect was large: After one year, the highest dose appeared to have reduced cortical amyloid close to the cutpoint of positivity. Get the latest information on their efforts and Alzheimer's risks here. author reply 2026-7 PubMed View Article Google The BSCL2 gene provides instructions for making a protein called seipin, whose function is unknown. The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Get a constantly updating feed of breaking news, fun stories, pics, memes, and videos just for you. From Ganfyd. PubMed | Google Scholar See all References and [11 C]PBB3. #adult T cell leukaemia/lymphoma 1. Today, several methods are available to isolate human monoclonal antibodies. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. While the human mAb, aducanumab, induced dose-dependent reduction in soluble and insoluble Aβ and slowed clinical decline in prodromal or mild AD patients, ARIA emerged as a major issue, limiting intravenous dosing . Nature 382, 685–691. nlm. PubMed citation; Articles by Description: Elenbecestat,also known as E2609 is a BACE1 inhibitor. Within cells, seipin is located in the membrane of a structure called the endoplasmic reticulum. Get research news & funding opportunities from the National Institute on Aging at NIH. In an attempt to prevent and/or reverse the disorder, we have partnered with industry leaders to study the effects and mechanisms of action of Alzheimer’s therapeutics, such as anti-Abeta immunotherapy, aducanumab, and the novel multimodal botanical extract DA-9803. , Shimada, H. John Hardy. Aducanumab are solanezumab are significantly better than 23 Apr 2018 Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β. If you take part in a clinical trial, you may be one of the first people to benefit from a new treatment. Three antibody-based drugs (crenezumab, gantenerumab, and aducanumab) are in clinical trials (2). By Melissa Bailey January 30, 2017. The limited number of treatment options has made Alzheimer's disease developed monoclonal antibody targeting Aβ is aducanumab by CrossRef PubMed PubMed Abstract: Aducanumab, a human-derived antibody targeting amyloid-β (Aβ), is in Phase 3 clinical trials for the treatment of Alzheimer's disease. 2003;24(2):419–29. 1038/nature22809. Sevigny J(1), Chiao P(1), Bussière T(1), Weinreb PH(1), Williams L(1), Clinical Development of Aducanumab, an Anti-Aβ Human Monoclonal Antibody Being Investigated for the Treatment of Early Alzheimer's Disease. Imbalance between the production and clearance of amyloid β (Aβ) peptides is considered to be the primary mechanism of AD pathogenesis. 2016 Nov;31(11):1631. Early studies showed decreased levels of beta-amyloid in the brains of study volunteers. PubMed Abstract: Aducanumab, a human-derived antibody targeting amyloid-β (Aβ), is in Phase 3 clinical trials for the treatment of Alzheimer's disease. Aducanumab gained significant press as recently as September 2016, Search Pubmed for. Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges. Page Content. PubMed PubMed Central Google Scholar Gispert S, et al. org/content/90/15_Supplement/S2. 2016 Oct 18;45 (4):717-718. PubMed articles Background: He has published journal papers, book chapters and abstracts in the area of cognitive neurology including dementia, Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease, Huntington's disease, chorea-acanthocytosis, frontal lobe disorders, inherited neurologic disorders, visual agnosia and optic aphasia. . gov? TREM2 deficiency reduces the efficacy of immunotherapeutic amyloid clearance. Efficacy and safety of anti‐amyloid‐β immunotherapy for Alzheimer's disease: a systematic review and network meta‐analysisAlzheimer’s disease (AD) (crenezumab, gantenerumab, and aducanumab) seem to be promising. Aducanumab are solanezumab are significantly better than Nov 11, 2018 PRIME is an ongoing Phase 1b study evaluating safety, tolerability, and PK/PD of aducanumab in patients (aged 50–90; positive amyloid PET Jun 21, 2017 Figure 1 of our original Article illustrated that treatment with aducanumab reduced human brain amyloid-β plaques in a dose-dependent Besides aducanumab, this trial evaluates the performance of proposed research . 2014. in 2016 PubMed cites ~4000 The antibody aducanumab reduces Abeta In recent years, several biomarkers for Alzheimer's disease have been developed, including assays for amyloid β and tau in the CSF, hippocampal atrophy on structural INTRODUCTIONAlzheimer’s disease and that aducanumab even RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Alzheimer's disease is a complicated disorder and, as several studies have shown, solely targeting Aβ might be a suboptimal treatment. Vaillancourt DE(1). However, every cloud has a silver lining. Current drug in research that targets beta-amyloid: Aducanumab. 2016 12 14; 36(50):12549-12558. The results showed the antibody readily transverses the blood–brain barrier and reduces Aβ aggregates in a time- and dosage-dependant manner. Acknowledgments: The authors are supported by NIH grants (AG046139, AG047266, AG005131). View Article PubMed PubMed Central Google Scholar;Sevigny J, Chiao P, Bussiere T, et al. What Is the Purpose of Trial Registration and Results Submission? Why Do I Need to Register My Trial and Submit Results to ClinicalTrials. Articles in PubMed by Thomas R. Safety and Efficacy of Anti-Amyloid-β Immunotherapy in Alzheimer’s Disease: 10. Epub 2016 Oct 14. Paclitaxel bound to bio-compatible proteins like albumin (Abraxane) is an injectable nano-suspension approved for the treatment of breast cancer. Posted by Nipun A quick search through the PubMed database reveals a few interesting cases of poisoning from kombucha tea consumption A Case of Hepatotoxicity Related to Kombucha Tea Consumption A case of Kombucha tea toxicity. View ORCID Profile David V. Although some antibodies for passive immunization are in clinical trials, passive immunization is not the only potential intervention strategy based on toxic Aβ and other antibodies may be more effective as passive immunizing agents. J Neurosci. RCT with Monoclonal antibodies from Pubmed Systematic reviews of Monoclonal antibodies from Pubmed Monoclonal antibodies in N Eng J Med, Lancet, JAMA, BMJ from Pubmed Evidence-Based Complementary and Alternative Medicine (eCAM) is an international peer-reviewed, Open Access journal that seeks to understand the sources and to encourage rigorous research in this new, yet ancient world of complementary and alternative medicine. aducanumab ligand page. Prev. Jump to: Systematic reviews of Monoclonal antibodies from Pubmed. Multiple Sclerosis. A multivariate therapy such as aducanumab that addresses both Aβ load as well as downstream neurochemical effects is likely a necessity for the treatment of AD. Brain barriers and brain fluid research in 2016: advances, challenges and controversies. The Root Cause of Alzheimer’s: Amyloid-beta and Tau prions. Therefore, calcium dynamics were used as a measure of functional outcome. Listing a study does not mean it has been evaluated by the U. During the double-blind, placebo-controlled phase, patients were randomized to fixed doses of aducanumab stratified by ApoE ɛ4 status and received aducanumab or placebo q4w for 52 weeks. s. In a recent issue of Nature, Sevigny et al. aducanumab and solanezumab are significantly The ACE gene provides instructions for making the angiotensin-converting enzyme. The monoclonal antibody aducanumab is the most advanced Alzheimer's drug in clinical trials—in Medline Plus, Clinical Trials, PubMed, Biochemical Data Summary More Info on this Drug View Label Archives , RxNorm , Get Label RSS Feed Microglia in Alzheimer’s disease. Nat Rev Drug Discov. Lancet Neurol. Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial. Immunotherapy with Aducanumab Restores Calcium Homeostasis in Tg2576 Mice. A OpenUrl CrossRef PubMed The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Posted by Nipun Chopra at 8:18 AM 2 comments:Chapter 7: Efficient Methods To Isolate Human Monoclonal Antibodies from Memory B Cells and Plasma Cells2 days ago · Well, there it is. Here are links to possibly useful sources of information about Aducanumab. Patients were randomized to fixed doses of aducanumab stratified by ApoE ɛ4 status. Apa; Standard; Harvard; Vancouver; Author;Is it possible to measure how much amyloid-beta is in your brain? http://www. Nanoparticles can be used in targeted drug delivery at the site of disease to improve the uptake of poorly soluble drugs [8, 9], the targeting of drugs to a specific site, and drug bioavailability. PubMed provides review articles from the past five years (limit to free review articles)Pubmed ID: 27582220. ncbi. Hanson, OpenUrl CrossRef PubMed Bevacizumab, sold under the trade name Avastin, is a medication used to treat a number of types of cancers and a specific eye disease. Biogen’s aducanumab, which in an early trial improved cognitive decline in a small number of patients. 35. Aducanumab Cmax, AUC0-last, and AUCinf increased in a dose-proportional manner. CNS inflammation and neurodegeneration Tanuja Chitnis and Howard L. Find out about Alzheimer's stages, causes and new treatments. Can walnuts protect against Alzheimer's disease? Certain blood pressure meds tied to lower Alzheimer's dementia risk ; Biogen shares tumble after key exec notes a changeup to pivotal aducanumab study due to ‘variability’ to add 510 patients to its pivotal study for the closely-watched drug aducanumab. The antibody aducanumab reduces Aβ OpenUrl CrossRef PubMed Web of Science Salloway S, Chen T, Ling Y et al (2016) The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. The manuscript has been seen and approved by all authors for submission to EJNMMI Research. Louis, Missouri, USA. Aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ, reduces soluble and insoluble Aβ in the brain, an action accompanied by a dose- Talk:Aducanumab Jump to navigation Here are links to possibly useful sources of information about Aducanumab. have been tested in early clinical trials: Bapineuzumab, Solenezumab, Gantenerumab, Crenezumab, Ponezumab, and Aducanumab OBJECTIVE: To describe the design of two Phase 3 studies evaluating efficacy and safety of aducanumab (BIIB037) in patients with Early Alzheimer’s disease (AD). Aducanumab; Alemtuzumab; Alirocumab; B. 00279 PubMed PubMedCentral Ling Y et al (2016) The antibody aducanumab reduces Aβ plaques in 1 day ago · I had no real expectations that aducanumab would work, despite all the attempts at positive spin over the years, and by golly, it doesn’t work. (2016) report findings from a phase 1b clinical trial of aducanumab (a monoclonal antibody targeting misfolded amyloid-β Aducanumab is a mAb that showed a dose‐ and time‐dependent reduction in amyloid plaques and a reduction in rate of cognitive decline on some (but not all) We present PubTree a hierarchical search tool that efficiently searches the PubMed/MEDLINE PubTree: A Hierarchical Search Tool for the of aducanumab, The NLM Drug Information Portal gives users a gateway to selected drug information from the National Library of Medicine and other key government agencies. Aducanumab (NCT02484547, NCT02477800) PubMed, and Embase with the About ScienceDirect Remote access Shopping cart Contact and support Terms and conditions There is still hope that solanezumab, aducanumab, PubMed: MeSH publication types. From MEDLINE®/PubMed®, a database of the U. PubMed/Medline; Google Scholar; Order Reprints; More by Aducanumab treatments have demonstrated beneficial effects in Aβ plaque clearing and a reverse calcium Footnotes ↵ ∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the Aducanumab restores calcium homeostasis in Tg2576 mice, 118 and also reduce soluble and insoluble Drug Targets, 2015 Search PubMed, Epub ahead of print. Nature. Several anti-Aβ antibodies have been tested in early clinical trials: Bapineuzumab, Solenezumab, Gantenerumab, Crenezumab, Ponezumab, and Aducanumab , among others. 2016; From MEDLINE®/PubMed®, a database of the U. Pharmacological and Toxicological Properties of the Potent Oral aducanumab, which showed a OpenUrl CrossRef PubMed In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal Aβ, and reduce sol. Arbor S Search in Google Scholar for. 2016;537(7618):50–6. This enzyme is able to cut (cleave) proteins. Arbor S; Access Statistics: Email Alert * PubMed 49. Exelon Patch is designed to deliver medication during the time it is worn. 1 day ago · I had no real expectations that aducanumab would work, despite all the attempts at positive spin over the years, and by golly, it doesn’t work. Background. , 2016). Methods. Xiaoguang Du 1, A phase Ib trial of aducanumab :2026. govNCT01397539). PubMed provides review articles from the past five years (limit to free review articles) The TRIP database provides clinical publications about evidence-based medicine. 7. Study of the Safety & Efficacy of Leukine® in the Treatment of Alzheimer's Disease The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. alzforum. View all comments by Pubmed on Aducanumab. Introduction. 2016; 537: 50-56. 1038/nature19323 pmid: 27582220. Induction of OpenUrl CrossRef PubMed Immunotherapy with Aducanumab Restores Calcium Homeostasis in Tg2576 Mice. We present PubTree a hierarchical search tool that efficiently searches the PubMed/MEDLINE dataset based upon a decision tree constructed using >26 million abstracts. PubMed | Scopus (30) | Google Scholar See all References An example is aducanumab, a human monoclonal antibody that aims to reduce amyloid-β and thus, ultimately, amyloid-related plaques. Aducanumab is an anti-amyloid-β antibody being developed for the treatment of AD. Passionate Immunotherapy with Aducanumab Restores Calcium Homeostasis in Tg2576 Mice. View Article PubMed PubMed al. This pathway subserves the flow of CSF into the brain along arterial perivascular spaces and subsequently into the brain interstitium, facilitated by aquaporin 4 (AQP4) water channels. PubMed; Google Scholar]. Aducanumab, a human monoclonal antibody selectively targeting aggregates and insoluble Aβ deposits, showed promising results in mice models and its PubMed Bu, G The glymphatic (glial-lymphatic) pathway is a fluid-clearance pathway identified in the rodent brain in 2012. Biogen and Eisai have announced just this morning that they're halting Phase III trials of aducanumab, their anti-amyloid antibody Immunotherapy targeting pyroglutamate-3 Aβ: prospects and challenges. The BSCL2 gene provides instructions for making a protein called seipin, whose function is unknown. Aducanumab Therapy Ameliorates Calcium Overload in a Mouse Model PubMed comprises more than 26 million citations for biomedical literature from MEDLINE, life science journals, and online books. Chan ES, Shetty MS, Sajikumar S, et al. Unfortunately, few trials have shown cognitive protection, leading to legitimate questions about the utility of Aβ42 as an AD target. Alzheimer’s disease hypothesis and related therapies. The antibody aducanumab reduces Abeta plaques in Alzheimer’s disease. Alzheimer’s disease: experimental models and reality. PubMed id: 29181491 Aducanumab (BIIB037), a human monoclonal antibody selective for aggregated forms of amyloid beta, is being investigated as a disease-modifying treatment for Alzheimer's disease (AD). Mol Cell Neurosci. Studies include clinical research on hemorrhage growth, diabetes, osteoporosis, etc. Try a different browser. A protocol amendment added a cohort of ApoE ɛ4 carriers who received aducanumab titrated to 10 mg/kg or placebo. Antibody-based immunotherapy against Aβ to trigger its clearance or mitigate its During the double-blind, placebo-controlled phase, patients were randomized to fixed doses of aducanumab stratified by ApoE ɛ4 status and received aducanumab or placebo q4w for 52 weeks. 36 Target engagement of this type is not sufficient to predict drug efficacy. 8 million, respectively, by 2030. neurology. PubMed Abstract: Aducanumab, a human-derived antibody targeting amyloid-β (Aβ), is in Phase 3 clinical trials for the treatment of Alzheimer's disease The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. TEXT AVAILABILITY 30 Oct 2017 reviewed from electronic databases (Cochrane library, Embase, Pubmed, and . CRISPR/Cas9-mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in neurodevelopment. co. nih. Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Castillo-Carranza Read the latest research on Alzheimer's disease. Stroke incidences and associated mortality are expected to rise to 23 million and 7. PubMed It's a fancy way of saying, the greater the amount of aducanumab given, the better the patients seemed to do. Aducanumab is one the last remaining late-stage Alzheimer’s drugs still in testing. on health & aging & Alzheimer's. Article; Aducanumab recognizes the N-terminus of the Aβ peptide. Interim analyses of a phase 1b clinical trial have suggested potential beneficial effects on amyloid pathology and cognitive status in patients treated with aducanumab (Sevigny et al. Skip to content Bloomberg the Company & Its Products Bloomberg Anywhere Remote Login Bloomberg Anywhere Login Biogen said it would add about 500 more patients to its studies of aducanumab Aducanumab is a recombinant human monoclonal antibody that selectively targets the amyloid-β (Aβ) peptide aggregates thought to play a part in the neurodegenerative process in Alzheimer's disease. Sevigny J Apr 23, 2018 Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β. #adult T-cell leukemia/lymphoma View this article via: JCI PubMed CrossRef Google Scholar Clayburgh DR, et al Aripiprazole is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT2), dopamine Type 2 (D2), 1 and 2 adrenergic, and H1 histaminergic receptors. Therapeutic potentials of plant iridoids in Alzheimer's and Parkinson's diseases: A review. Read about new data from the long-term extension of Biogen's ongoing Phase 1b study showing that aducanumab reduces amyloid plaques in Alzheimer's patients. Aducanumab (BIIB037), an anti-amyloid beta monoclonal antibody, in patients with prodromal or mild Alzheimer’s disease: Interim results of a randomized, double-blind, placebo-controlled, phase Aisen is an advisor and receives consulting fees from Biogen regarding aducanumab but is not involved with the current trial. 2016;537(7618) PubMed; 65. Exercise in Adults with Mild Memory Problems (EXERT) Purpose: To evaluate the effects of physical exercise on cognition, functional status, brain atrophy, blood flow, and cerebrospinal fluid biomarkers of Alzheimer's disease in adults with a mild memory impairment. PubMed Health. Addendum: The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. Biogen, a Cambridge, Massachusetts biotech company, announced last week that early tests of their new drug aducanumab, a monoclonal antibody, had shown impressive results in treating those with early stage Alzheimer’s disease. Replace the new patch the next day at the same time as usual. Impact of Reference/Target Region Selection on Amyloid PET Standard Uptake Value Ratios in the Phase 1b PRIME Study of Aducanumab. Aducanumab and solanezumab improve the cognitive function, while aducanumab and bapineuzumab may increase the risks of ARIA. nlm. [PMC free article] [PubMed]. Biogen shares tumble after key exec notes a changeup to pivotal aducanumab study due to ‘variability’ to add 510 patients to its pivotal study for the closely-watched drug aducanumab. Select a topic, define your favourite journals, and you will receive the weekly AMEDEO literature newsletters. uk) submitted 2 years ago by brainstorm11 Nootropedia 30 comments Clinical Trial Registry Numbers in MEDLINE ® /PubMed ® Records Go to PubMed A clinical trial is a research study using human volunteers to answer specific health questions. A phase Ib trial of aducanumab (Biogen) PubMed CrossRef Google Scholar. Aducanumab in Cochrane Collaboration. Abstract Alzheimer’s disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Search for other works by this author on: The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. S. Here we report the generation of aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ. DFMO and Arginine Arginine is one of the 20 amino acids used to build proteins, and it has been found that the AD brain consumes inordinate quantities of arginine . 748ps have appeared in the PubMed under the keyword ‘Alzheimer’sdisease,’ 30% more ps Clinical trials help doctors understand how to treat a particular disease or condition. A schematic comparison of untargeted and targeted drug delivery systems is shown in Figure 1. Pubmed link: Link to original study. There is a small risk of false positives inciting anxiety and/or depression in non-demented people. Biogen and Eisai Announce Presentation of Detailed Analyses from the Phase 1b Long-Term Extension Study of Aducanumab at Clinical Trials on Alzheimer’s Disease (CTAD)Here we report the generation of aducanumab, a human monoclonal antibody that selectively targets aggregated Aβ. ” Design of nanotechnology – based drug delivery Systems. gov/pubmed How does the new alzheimer's drug aducanumab differ from Aducanumab decreased Aβ detectable by PET scan in a dose- and time-dependent manner, an effect not seen in patients treated with placebo. Crossref; PubMed; Scopus (462) Google Scholar; PubMed; Scopus (27)Category:Monoclonal antibodies. #adult T-cell leukemia/lymphoma View this article via: PubMed CrossRef Google Scholar Nürnberger W, Michelmann Therapies that reduce the abundance or disrupt the oligomerization of a modified form of amyloid-beta may treat Alzheimer's disease patientsLu AE58054 Added to Donepezil for the Treatment for The "NLM Curated PubMed Citations" section links to all PubMed records that are tagged with the same MeSH term Here are links to possibly useful sources of information about Aducanumab. Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly Organize Save any article or search result from DeepDyve, PubMed, and Google Scholar all in one place. Authors: Jeff Sevigny, Ping Chiao, one year of monthly intravenous infusions of aducanumab reduces brain Aβ in a dose- and time-dependent Request PDF on ResearchGate | On Jul 1, 2015, Jeff Sevigny and others published Aducanumab (BIIB037), an anti-amyloid beta monoclonal antibody, in patients with Efficacy and safety of anti-amyloid-β immunotherapy for Alzheimer's disease: aducanumab and solanezumab in Alzheimer's disease: a systematic review Alzheimer’s disease hypothesis and related therapies. Budd Haeberlein, S. Acknowledgments This work was supported by the Medical Research Fund of Guangdong Province (A2015481), Traditional Chinese Medicine Research Projects of Guangdong Province (20171152), and Doctoral Research Fund of PubMed Abstract: Aducanumab, a human-derived antibody targeting amyloid-β (Aβ), is in Phase 3 clinical trials for the treatment of Alzheimer's disease Alzheimer’s disease (AD) is a major form of senile dementia, characterized by progressive memory and neuronal loss combined with cognitive impairment. (2015, March 20). 2016 Sep 1;537(7618):50-6. The IUPHAR/BPS Guide to Pharmacology. By inhibiting BACE, a key enzyme in the production of Aβ peptides, E2609 decreases the formation of these peptides which can aggregate into toxic oligomers and protofibrils and eventually form amyloid plaques in the brain. Biogen Drops After Alzheimer's Drug Trial Change Raises Concerns. Within cells, seipin is located in the membrane of a structure The BDNF gene provides instructions for making a protein found in the brain and spinal cord called Citation on PubMed or Free article on PubMed Central. Immunity. Further, the aging population, imbalanced lifestyles, and environmental factors continue to shift the rate of Hampel H, Frank R, Broich K, Teipel SJ, Katz RG, Hardy J, et al. Transgenic mice expressing mutant A53T human alpha-synuclein show neuronal dysfunction in the absence of aggregate formation. This amyloid hypothesis is supported by the recent success of the human anti‐amyloid antibody aducanumab, in clearing plaque and slowing clinical impairment in prodromal or mild patients in a phase Ib trial. Alzheimer's disease (AD) is characterized by deposition of amyloid-β (Aβ) plaques and neurofibrillary tangles in the brain, accompanied by synaptic dysfunction and neurodegeneration. Cited by: 776Publish Year: 2016Author: Sevigny J, Chiao P, Bussière T, Weinreb Ph, Williams L, Maier M, Dunstan R, Salloway S, Chen T, LingAducanumab | ALZFORUMhttps://www. In patients with prodromal or mild AD, one year of monthly i. et al (2015) Aducanumab (BIIB037), an anti-amyloid beta monoclonal antibody, in patients The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology OpenUrl CrossRef PubMed Web of . In this study, 165 patients with clinical AD diagnosis and positive Aβ PET scan were given monthly doses of 1, 3, 6 or 10 mg kg −1 of aducanumab over the course of a year. F1000Prime Recommended Article: The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. This latter finding led the authors to suggest that microglia, brain-resident macrophages, are responsible for Aβ clearance. AD is the most common neurodegenerative disease worldwide, affecting one-fifth of those aged over 85 years. View all comments by As for Alzheimer’s disease, the possible value of passive immunotherapy with agents such as aducanumab is considered to be a potential disease-modifying approach that could slow or halt the progressive decline associated with this devastating disorder. aducanumab pubmedSep 1, 2016 The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. By Derek Lowe 15 adding more patients to their Phase III trial of their antibody aducanumab. Aducanumab dose-dependently reduced amyloid deposition in six cortical regions of the brain. View Article PubMed Google Scholar; Chu PC, Chai WY, Tsai CH, Kang ST, Yeh CK, Liu HL. Biogen IDEC Presents Positive Interim Results From Phase 1B study at 2015 AD/PD Conference: Aducanumab (BIIB037) Reduced Brain Amyloid Plaque Levels and Slowed Cognitive Decline in Patients with Prodromal or Mild Alzheimer’s disease. Articles in PubMed by Thomas R The NLM Drug Information Portal gives users a gateway to selected drug information from the National Library of Medicine and other key government agencies. Cited in PubMed PMID: 26882285. More than 49,000 drugs can be searched. Some of these immunotherapeutic approaches failed to show significant clinical benefits in the mild-to-moderate AD patients being treated, for reasons that are not known. This randomized, double-blind, placebo-controlled single ascending-dose study investigated the safety, tolerability, and pharmacokinetics (PK) of aducanumab Aripiprazole is a quinoline derivate and atypical anti-psychotic agent. Brain barriers and brain fluid research in 2016: advances, challenges and controversies. Sevigny J 11 Nov 2018 PRIME is an ongoing Phase 1b study evaluating safety, tolerability, and PK/PD of aducanumab in patients (aged 50–90; positive amyloid PET 1 Jun 2018 Recently published results of a phase one trial of aducanumab, a human monocloncal antibody that selectively . PubMed PubMed Central Google Scholar;Caraci F, Leggio GM, Salomone S and Drago F. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs. Journal Article; Review; Cite this. “CNS is a lifesaver! Not only do they give you medication, but they also educate you, have you visit with doctors, therapists, and every array of medical professional you will need for whatever condition you’re doing your medical trial on. Also, get information about managing complications of Parkinson’s such as Kastanenka KV, Bussiere T, Shakerdge N, Qian F, Weinreb PH, Rhodes K, Bacskai BJ. org/therapeutics/aducanumabAducanumab dose-dependently reduced amyloid deposition in six cortical regions of the brain. In this review we discussed recent developments in nanotechnology for drug delivery. ↵ ∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. More than ClinicalTrials. It is in Phase III testing to treat Alzheimer's disease and is a member of the EMEA's PRIority MEdicines scheme for breakthrough therapies. A Aducanumab Will Proceed to Phase 3 Trial P. Learn about Alzheimer's symptoms such as memory loss and senile dementia. uk/science/2016/09/01/alzheimers-new-drugPatients treated with the highest dose of aducanumab saw an almost complete clearance of the amyloid plaques which prevent brain cells communicatingRead about new data from the long-term extension of Biogen's ongoing Phase 1b study showing that aducanumab reduces amyloid plaques in Alzheimer's patients. Back to TopImpact of Reference/Target Region Selection on Amyloid PET Standard Uptake Value Ratios in the Phase 1b PRIME Study of AducanumabHowever, every cloud has a silver lining. [Epub ahead of print]. PubMed PMID: 29780864; PubMed Central PMCID: PMC5956814. 1136/jnnp-2014-309493 PubMed The antibody aducanumab reduces Abeta Read "Aducanumab (BIIB037), an anti-amyloid beta monoclonal antibody, in patients with prodromal or mild Alzheimer’s disease: Interim results of a randomized The New England Journal of Medicine (NEJM) is a weekly general medical journal that publishes new medical research and review articles, and editorial opinion on a Immunotherapy for Alzheimer’s disease (AD) remains promising in the improvement of cognition and memory via the clearing of amyloid-β protein (Aβ) in the AD brain PubTree: A ierarchical Search Tool for the PubTree a hierarchical search tool that efficiently searches the PubMed/MEDLINE of aducanumab in the Despite continuing debate about the amyloid β‐protein (or Aβ hypothesis, new lines of evidence from laboratories and clinics worldwide support the concept that an Despite continuing debate about the amyloid β‐protein (or Aβ hypothesis, new lines of evidence from laboratories and clinics worldwide support the concept that an Aβ antibodies (aducanumab, BAN2401, OpenUrl CrossRef PubMed. Setbacks Biogen shares tumble after key exec notes a changeup to pivotal aducanumab study due to ‘variability’The IUPHAR/BPS Guide to Pharmacology. 1002/mds. and insol. View Article: Google Scholar: PubMed/NCBI 45 Wang J, Chen L, Jin S, Lin J, Zheng H, Zhang H, Fan H, He F, Ma S and Li Q: Altered expression of microRNA-98 in IL-1β-induced cartilage degradation and its role in chondrocyte apoptosis. Related articles in PubMed. Nature 2016; 537: 50 – 56 doi: 10. APP mouse models for Alzheimer's disease preclinical studies humans is the preclinical testing of the anti‐Aβ antibody aducanumab. Authors: James Ferrero, Leslie In this single-dose study, aducanumab demonstrated an acceptable safety and tolerability profile and linear PK Abstract Background Low-molecular-weight heparin is the standard treatment for cancer-associated venous thromboembolism. v. Learn about the various ways Parkinson’s disease is treated, including medication and surgery. Dr. Sevigny J(1), Chiao P(1 Cited by: 776Publish Year: 2016Author: Sevigny J, Chiao P, Bussière T, Weinreb Ph, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Lingaducanumab - PubMed - NCBIhttps://www. 5/2/2019 · #Aducanumab 1. Google Scholar. 2017 Apr 26;37(17):4430-4432. So while previous trials targeted patients in stages 4+, aducanumab is being given to patients with stage 3 disease. TEXT AVAILABILITY Nature. Two Phase 3 studies are under way to test whether monthly doses of aducanumab can slow cognitive and functional decline in people with early Alzheimer’s disease. 221AD301 Phase 3 Study of Aducanumab (BIIB037) PubMed; Neural Connectivity in Syntactic Movement Processing. The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. PubMed 54. CrossRef PubMed. Parallel-Group Study to Evaluate the Efficacy and Safety of Aducanumab (BIIB037)in Subjects with Early Alzheimer's DiseasePI The fonts could not be downloaded because of your browser settings. co. Review Bioclinica clinical trial studies here. a recent clinical trial using Aducanumab indicated that significant amyloid removal Amedeo offers weekly literature overviews in scientific medicine. Aβ in a dose-dependent manner. Biogen and Eisai have deepened their partnership by agreeing to work together on the continued development of the Alzheimer’s therapy aducanumab (BIIB037), which targets harmful beta amyloid protein clusters. It may benefit you, or others like you, in the future. International Journal of Alzheimer’s Disease is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of Alzheimer's disease. Nature 2016; Articles in PubMed by Fan Liao;APP mouse models for Alzheimer's disease preclinical studies. Aducanumab reduces Aβ plaques in Alzheimer's disease. Aducanumab is a treatment made up of antibodies, tiny y-shaped proteins that latch on to dangerous substances in the body, acting like flags, showing the immune system what to clear away. Systematic reviews of Aducanumab. J. aducanumab, a co-development of View Article PubMed PubMed Central Google Scholar;Pubmed ID: 29067304. Dementia is a clinical syndrome characterized by progressive decline in two or more cognitive domains, including memory, language, executive and visuospatial function, personality, and behavior, which causes loss of abilities to perform instrumental and/or basic activities of daily living. The first efficient method described was the panning of phage display libraries constructed from the Ig variable genes of immunized or infected individuals ( 1 ) or from random synthetic libraries ( 2 ). View Abstract. 26833. Conversely, there are a number of potential negative aspects of early dementia screening. Acute topical application of aducanumab to the brain resulted in clearance of amyloid plaques. Just this year, a new drug called Aducanumab, aka BIIB037, was reported to be effective in reversing cognitive decline in small, initial trials with human trials–not just mice. et al. In a transgenic mouse model of AD, Disease modifying therapies (DMTs) are urgently needed for neurodegenerative diseases (NDD) such as Alzheimer’s disease (AD) and many other disorders characterized eisai's news release u. PubMed provides review articles from the past five Read about Biogen and Eisai agreeing to work together to continue developing the Alzheimer's treatment aducanumab, which targets harmful protein clusters. Wang P, Lin M, Pedrosa E, et al. Aripiprazole has partial agonistic activity at dopamine D2 receptors and serotonin 5-HT1A Aducanumab, a human monoclonal antibody selectively targeting aggregates and insoluble Aβ deposits, showed promising results in mice models and its PubMed Bu, G More Rough Alzheimer’s News. OpenUrl CrossRef PubMed Sevigny J , Chiao P , Bussière T , Weinreb PH , Williams L , Maier M , Dunstan R , Salloway S , Chen T , Ling Y , O'Gorman J , Qian F , Arastu M , Li M , Chollate S , Brennan MS , Quintero‐Monzon O , Scannevin RH , Arnold HM , Engber T et al ( 2016 ) The antibody aducanumab reduces Aβ plaques in Alzheimer's disease . The group met once and was led through a pre-specified agenda by the three co-chairs MNR, AB, and CWR. Find science-based info. Between March 1, and Sept 15, 2015, we searched the Cochrane Library, PubMed, and Embase with the search term “Alzheimer's Disease” in combination with the terms “pathology”, “imaging”, “diagnosis”, “therapy”, “trials”, “epidemiology”, “CSF”, and “biomarkers” for articles published in any language since Jan 1 Unfortunately, few trials have shown cognitive protection, leading to legitimate questions about the utility of Aβ42 as an AD target. 3. 17: Chiao P, Bedell BJ, Avants B, Zijdenbos AP, Grand'Maison M, O'Neill P, O'Gorman J, Chen T, Koeppe R. PubMed The ARIA issue recently generated increasing interest after the very promising data for the Phase 1b study of aducanumab (NCT01677572) were PubMed Abstract PubMed/Medline; Google Scholar; Order Reprints; More by Authors. Footnotes. Federal Government. CrossRef PubMed Web of Sevigny J, Chiao P, Bussière T, Weinreb PH, Williams L, Maier M, Dunstan R, Salloway S, Chen T, Ling Y, O'Gorman J, Qian F, Arastu M, Li M, Chollate S, Brennan MS, Quintero-Monzon O, Scannevin RH, Arnold HM, Engber T, Rhodes K, Ferrero J, Hang Y, Mikulskis A, Grimm J, Hock C, Nitsch RM, Sandrock A Addendum: The antibody aducanumab reduces Aβ In mice overexpressing amyloid precursor protein, aducanumab showed a minimal effective dose of 3 mg/kg upon weekly systemic administration consistent with the clinical doses, leading to dose- and time-dependent reductions in brain amyloid load and evidence of slowing of clinical decline in prodromal patients or those with mild Alzheimer’s Neurimmune. The ARIA issue recently generated increasing interest after the very promising data for the Phase 1b study of aducanumab (NCT01677572) were presented at the 12 th AD/PD Meeting in Nice ( 19) and at the Alzheimer’s Association International Conference (AAIC 2015) in Washington ( 12 ). gov is an ICMJE-acceptable public registry, offering up-to-date information for locating clinical trials for a wide range of diseases and conditions The antibody aducanumab reduces Aβ plaques in Alzheimer's disease. In this single-dose study, aducanumab demonstrated an acceptable safety and tolerability profile and linear PK at doses ≤30 mg/kg (clinicaltrials. Bart De Strooper. Albert MS, DeKosky ST, Dickson D, Dubois B, 15/2/2018 · In a presentation to investors Wednesday, Biogen said it would add about 500 more patients to its studies of aducanumab, which is in the final stages of Author: Bailey Lipschultz, Rebecca SpaldingPhone: (212) 318-2000Location: 731 Lexington Avenue, New York, 10022, NYAducanumab 36-month data from PRIME: a randomized, double n. In a transgenic mouse model of AD, aducanumab is shown to enter the brain, bind parenchymal Aβ, and reduce soluble and insoluble Aβ in a dose-dependent manner. 1 Department of Neurology, Hope Center for Neurological Disorders, Charles F. Biogen's antibody, aducanumab, set the Alzheimer's community abuzz this spring, when the company reported that 27 people with mild Alzheimer's who took a 10-mg dose of the drug showed significant cognitive benefits over controls, as well as reduced levels of β amyloid in PET brain scans. in 2016 PubMed cites ~4000 papers on CSF, ~2950 papers on the blood News Article Aducanumab: Alzheimer's drug "best news for dementia in 25 years" (telegraph. Sevigny, J. Why Should I Register and Submit Results? Contents. Alzheimer's Disease as a Neurovascular Inflammatory Disorder. fda confirms sufficient data to advance investigational bace inhibitor e2609 for treatment of early alzheimer's disease to phase Ⅲ is posted. gov/pubmed Aisen is an advisor and receives consulting fees from Biogen regarding aducanumab but is not involved with the current trial. Antibody dependent cell- mediated phagocytosis is a critical Fc effector mechanism by which antibodies can clear such proteins and the ability to reliably measure phagocytosis events mediated by antibodies is of great value. ” In the past decade, Alzheimer’s disease drug discovery has been directed at ‘disease modifying drugs’ that are able to counteract the progression of Alzheimer’s disease by intervening in specific parts of its neuropathological process. 1523/JNEUROSCI. That doesn’t make me a prophet – I think any objective observer would have to have come to the same conclusion. Update in Nature. on DOAJ; on Google Scholar on PubMed; Export Article Aducanumab). gov/pubmed?term=aducanumab&cmd=DetailsSearchPubMed comprises more than 26 million citations for biomedical literature from MEDLINE, life science journals, and online books. Tau. Arndt JW(1), Qian F(2), Smith BA(2), Quan C(2) Oct 30, 2017 reviewed from electronic databases (Cochrane library, Embase, Pubmed, and . Xiaoguang Du 1, PubMed PubMed Central View Article Biogen's aducanumab raises hope that Alzheimer's #Aducanumab 1. Other potential sources include: Centre for Reviews and Dissemination and CDC Aducanumab is a human recombinant anti-beta amyloid monoclonal antibody. 1/9/2016 · 1. Treatment & Care. The problem seems to have been that the tests were creating too much statistical noise, and not giving researchers a clear indication of whether or not the drug was helping patients. Clinical Development of Aducanumab, an Anti-Aβ Human Monoclonal Antibody Being Investigated for the Treatment of Early Alzheimer's Disease