{"title":"Optimizing Antibody-Based Therapies for Alzheimer's Disease: From Clinical Limitations to Molecular Engineering Innovations.","authors":"Qian Liu, Rong-Rong Lin","doi":"10.14336/AD.2026.0292","DOIUrl":null,"url":null,"abstract":"<p><p>Antibody-based immunotherapy represents one of the most promising disease-modifying strategies for Alzheimer's disease (AD). Recent anti-amyloid-β (Aβ) antibodies have achieved robust plaque clearance and modest cognitive benefits in early AD, establishing clinical proof of concept. However, limited efficacy and safety concerns, particularly amyloid-related imaging abnormalities (ARIA), continue to restrict their therapeutic potential. This review outlines the current clinical status of antibody therapies targeting Aβ, tau, and neuroinflammatory pathways, and summarizes key antibody optimization strategies, including aggregation-state-selective targeting, Fc engineering, brain shuttle technologies, nanobody platforms, and nanotechnology-enabled delivery. We further discuss emerging concepts from tumor immunotherapy, such as antibody-guided protein degradation and conditionally active biologics, as potential avenues for next-generation AD treatment.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6000,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging and Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.14336/AD.2026.0292","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Antibody-based immunotherapy represents one of the most promising disease-modifying strategies for Alzheimer's disease (AD). Recent anti-amyloid-β (Aβ) antibodies have achieved robust plaque clearance and modest cognitive benefits in early AD, establishing clinical proof of concept. However, limited efficacy and safety concerns, particularly amyloid-related imaging abnormalities (ARIA), continue to restrict their therapeutic potential. This review outlines the current clinical status of antibody therapies targeting Aβ, tau, and neuroinflammatory pathways, and summarizes key antibody optimization strategies, including aggregation-state-selective targeting, Fc engineering, brain shuttle technologies, nanobody platforms, and nanotechnology-enabled delivery. We further discuss emerging concepts from tumor immunotherapy, such as antibody-guided protein degradation and conditionally active biologics, as potential avenues for next-generation AD treatment.
期刊介绍：
Aging & Disease (A&D) is an open-access online journal dedicated to publishing groundbreaking research on the biology of aging, the pathophysiology of age-related diseases, and innovative therapies for conditions affecting the elderly. The scope encompasses various diseases such as Stroke, Alzheimer's disease, Parkinson’s disease, Epilepsy, Dementia, Depression, Cardiovascular Disease, Cancer, Arthritis, Cataract, Osteoporosis, Diabetes, and Hypertension. The journal welcomes studies involving animal models as well as human tissues or cells.
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