{"title":"Perspective: Minimally clinically important “symptomatic” benefit associated with disease modification resulting from anti-amyloid immunotherapy","authors":"John Alam, Marwan N. Sabbagh","doi":"10.1002/trc2.70035","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <p>Despite some skepticism regarding the amyloid hypothesis, there is growing evidence that clearing amyloid by targeting specific species of amyloid (plaque, oligomers, fibrils, and protofibrils) for removal has therapeutic benefits. Specifically, there is growing evidence that, in mild cognitive impairment and mild dementia due to Alzheimer's disease (AD), robust and aggressive removal of amyloid can slow cognitive decline as measured by global instruments, composite measures, and cognitive testing. Furthermore, clinical efficacy signals coupled with clear biomarker changes provide the first evidence of disease modification. This effect seems to be in addition to symptomatic treatments and opens speculation that the effect of anti-amyloid monoclonal antibodies might be clinically meaningful through symptomatic amelioration that is a result of disease modification.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Clearance of brain amyloid plaques may lead to a clinical benefit in patients with early AD.</li>\n \n <li>Aggregated Aβ may play a role in both disease expression and progression.</li>\n \n <li>Anti-amyloid monoclonal antibodies might be clinically meaningful through symptomatic amelioration resulting from disease modification.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11746071/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/trc2.70035","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Despite some skepticism regarding the amyloid hypothesis, there is growing evidence that clearing amyloid by targeting specific species of amyloid (plaque, oligomers, fibrils, and protofibrils) for removal has therapeutic benefits. Specifically, there is growing evidence that, in mild cognitive impairment and mild dementia due to Alzheimer's disease (AD), robust and aggressive removal of amyloid can slow cognitive decline as measured by global instruments, composite measures, and cognitive testing. Furthermore, clinical efficacy signals coupled with clear biomarker changes provide the first evidence of disease modification. This effect seems to be in addition to symptomatic treatments and opens speculation that the effect of anti-amyloid monoclonal antibodies might be clinically meaningful through symptomatic amelioration that is a result of disease modification.
Highlights
Clearance of brain amyloid plaques may lead to a clinical benefit in patients with early AD.
Aggregated Aβ may play a role in both disease expression and progression.
Anti-amyloid monoclonal antibodies might be clinically meaningful through symptomatic amelioration resulting from disease modification.
期刊介绍:
Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.