Aduhelm (aducanumab) / Neurimmune, Eisai - LARVOL DELTA

The structural foundations of anti-amyloid-β immunotherapies: Unravelling antibody-antigen interactions in Alzheimer's disease treatment. (PubMed, J Alzheimers Dis) - "BackgroundAnti-amyloid-β (Aβ) immunotherapies are emerging as treatments for Alzheimer's disease (AD).ObjectiveThis review examines the structure-activity relationships of anti-Aβ therapeutics tested in phase 3 trials.MethodsWe analyzed crystallographic data and molecular models to elucidate the Aβ binding mechanisms of donanemab, lecanemab, aducanumab, bapineuzumab, gantenerumab, solanezumab, and crenezumab.ResultsLecanemab recognizes minimally degraded Aβ missing 1-2 residues, avoiding common Aβ in circulation and further degraded material sequestered in plaques. This focal point may account for the significant cognitive effects of lecanemab. The structure of aducanumab suggests a broadly neutralizing role has evolved for natural immunity to AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Vascular Neurology • APOE

From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer's Disease Landscape. (PubMed, Medicina (Kaunas)) - "Aducanumab and Lecanemab are IgG1 monoclonal antibodies that retard the progression of AD. Novel monoclonal antibodies may halt the AD course. Advances in delivery systems across the BBB are promising for the efficacy of AD treatments."

Journal • Review • Alzheimer's Disease • CNS Disorders • Gene Therapies • Inflammation • Metabolic Disorders • APOE • Aβ42

Reducing ARIA risk in Alzheimer's disease: Real-world impact of APOE genotype-guided slow titration with aducanumab and lecanemab. (PubMed, J Alzheimers Dis) - "Plaque clearance was achieved in 50% of evaluable aducanumab patients and 26.3% of lecanemab patients. Compared to clinical trial ARIA rates, our results suggest that individualized, genotype-informed titration improves safety although plaque clearance rates were less robust."

Journal • Real-world evidence • Alzheimer's Disease • CNS Disorders • APOE

Lower baseline amyloid beta burden is associated with greater percent of amyloid beta positron emission tomography reduction and better clinical outcomes in the aducanumab Phase 3 trials ENGAGE and EMERGE in early Alzheimer's disease. (PubMed, J Prev Alzheimers Dis) - P3 | "The relationship between baseline amyloid beta load and treatment benefit in a large population after exposure to an amyloid beta-directed antibody provides insight into which subpopulations are likely to benefit from this class of treatment."

Clinical data • Journal • P3 data • Alzheimer's Disease • CNS Disorders

Early intervention anti-Aβ immunotherapy attenuates microglial activation without inducing exhaustion at residual plaques. (PubMed, Mol Neurodegener) - "These findings demonstrate that chronic early intervention by an anti-amyloid immunotherapy leads to a dose-dependent decrease in plaque formation, which is associated with lower brain-wide microglial DAM activation and neurodegeneration. Microglia at residual plaques still display a combined DAM and antigen-presenting phenotype that suggests a continued treatment response."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders

Evaluation of Amyloid Removal as a Surrogate for Cognitive Decline: Pilot Analysis in Individual-Level Data from the A4 Study of Solanezumab. (PubMed, medRxiv) - "Amyloid removal has been used as a surrogate outcome in Alzheimer's disease trials, allowing accelerated approval of aducanumab and lecanemab. Estimates showing near-zero effects of amyloid reduction on cognitive decline suggest minimal impact of amyloid reduction in populations with little disease progression. Replication in anti-amyloid trials with larger treatment effects could guide treatment and regulatory decisions."

Journal • Alzheimer's Disease • CNS Disorders

Aducanumab binds high molecular weight soluble Aβ oligomers and restores intracellular calcium levels. (PubMed, Alzheimers Res Ther) - "Our findings demonstrate that aducanumab specifically targets HMW AβOs, mitigating their neurotoxic effects by restoring intracellular calcium homeostasis. These results provide mechanistic insight into aducanumab's therapeutic action and support its potential role in modifying AD pathology by selectively neutralizing Aβ species."

Journal • Alzheimer's Disease • CNS Disorders • Aβ42

The Therapeutic Potential of Butyrate and Lauric Acid in Modulating Glial and Neuronal Activity in Alzheimer's Disease. (PubMed, Nutrients) - "While amyloid-targeting therapies like Aducanumab and Lecanemab show some promise, their efficacy remains limited. Both compounds have been shown to decrease amyloid-β deposition, reduce neuroinflammation, and promote neuroprotection in AD models. This review explores the mechanisms through which butyrate and lauric acid modulate glial and neuronal activity, highlighting their potential as therapeutic agents for mitigating neuroinflammation and slowing AD progression."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation

Analytical development and application of a targeted liquid chromatography-tandem mass spectrometry assay for chimeric aducanumab. (PubMed, MAbs) - "The fit-for-purpose assay was successfully applied to quantify chAdu in both mouse cortex and plasma samples obtained from a pilot pharmacokinetic study of a mouse model of amyloid plaque deposition. This targeted mass spectrometry workflow offers a robust and reproducible alternative to ELISA for preclinical biotherapeutic analysis, particularly when dealing with complex biological samples."

Journal • Alzheimer's Disease • CNS Disorders

Unveiling Aducanumab's safety profile: A comprehensive pharmacovigilance analysis. (PubMed, PLoS One) - "Strength: Utilized multiple signal detection algorithms (ROR, PRR, BCPNN, MGPS) to enhance robustness of pharmacovigilance findings. Limitation: Reliance on spontaneous FAERS reports, which are prone to underreporting, overreporting, and reporting bias."

Adverse events • Journal • Retrospective data • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Mental Retardation • Psychiatry

Recent Advances in Antibody Therapy for Alzheimer's Disease: Focus on Bispecific Antibodies. (PubMed, Int J Mol Sci) - "The regulatory approval of three anti-amyloid monoclonal antibodies (mAbs), including aducanumab, lecanemab, and donanemab, has established immunotherapy as a therapeutic approach to modify disease progression. This review combines existing information about antibody-based therapy in AD by focusing on bispecific antibody formats and their preclinical and clinical development, as well as biomarker-based patient selection and upcoming combination strategies. The combination of rationally designed bispecific antibodies with fluid and imaging biomarkers could show potential for overcoming existing therapeutic challenges and delivering significant clinical advantages."

IO biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation

Alzheimer's disease basics: we all should know. (PubMed, Neurol Res) - "Additionally, recent clinical trial data of anti-Aβ monoclonal antibodies (aducanumab, lecanemab, donanemab) were reviewed, with comparative analysis of efficacy, safety, and trial outcomes. While mAb therapies mark progress in disease modification, their success depends on patient stratification, early intervention, and safety profiling. Future directions must emphasize combinatorial and personalized approaches incorporating early biomarkers, neuroimaging, and emerging technologies to effectively combat the rising global burden of AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Inflammation • APOE • MAPT

A bibliometric analysis of the current research status and hotspots regarding Aducanumab treatment for Alzheimer's disease. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "This study employs bibliometric methods to reveal the publication trends related to Aducanumab in the context of Alzheimer's disease, examining collaborations among countries, regions, and authors, as well as recent research hotspots. It provides objective data that serves as a reference for scientific research and clinical practice concerning Aducanumab treatment for Alzheimer's disease."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

A Systematic Review of the Efficacy and Safety of Anti-amyloid Monoclonal Antibodies in Alzheimer's Disease. (PubMed, Cureus) - "Aducanumab showed dose-dependent effects on plaque clearance but had inconsistent cognitive outcomes and higher ARIA rates. Recent mAb trials provide promising evidence for disease modification in early AD stages, particularly with lecanemab and donanemab. However, variability in cognitive outcomes and safety concerns warrant cautious interpretation and long-term validation."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Current clinical trends in developing strategies for dementia disorders and the role of Korean Red Ginseng. (PubMed, J Ginseng Res) - "Recently, the development of the FDA approved monoclonal antibodies (mAbs) targeting amyloid proteins, such as aducanumab, lecanemab, and donanemab, etc. Although these are in initial stage, developing mAbs is believed to proposed as next stage of AD therapeutics. Additionally, pleiotropic phenomena of KRG, not only cognition but also overall human health systems, warranting further underling medical evidence. These efficacies and multi-effectiveness can be a high potential candidate for the current trends in developing strategies for dementia disorders."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Is US residence a risk factor for Alzheimer's disease? (PubMed, J Alzheimers Dis) - "It is around 0.7% in the UK, 0.9% in Denmark, and worldwide the estimate is 0.5%. Alongside risk factor reduction, the Centers for Medicare and Medicaid Services could strengthen the US fight against AD by reconsidering its October 2023 decision to liberalize reimbursement of amyloid PET scans, or better yet, advise replacing these non-specific scans with FDG-PET, which shows what AD is really about: impaired regional brain function."

Journal • Alzheimer's Disease • CNS Disorders

Management of Patients With Mild Cognitive Impairment in the Era of Anti-Amyloid Therapy: A Worldwide Neurology Survey. (PubMed, Neurol Clin Pract) - "We performed a worldwide electronic survey of neurology practitioners through the Practice Current section of Neurology® Clinical Practice with clinical and practice-related questions in November 2019-August 2021 and repeated it in May-October 2023 after the FDA's approval of aducanumab and lecanemab but before the approval of donanemab. Our results highlight practice differences among cognitive subspecialists and other practitioners worldwide in the management of MCI. Attitudes toward anti-amyloid therapy indicate cautious optimism, with concerns about side effects but a general interest to prescribe."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Evaluation of cognitive, functional, and behavioral effects observed in EMERGE, a phase 3 trial of aducanumab in people with early Alzheimer's disease. (PubMed, Alzheimers Dement) - P3 | "Endpoints in EMERGE assessed different aspects of cognition, daily function, and behavioral symptoms. Treatment benefits were observed across subdomains on all five clinical endpoints. Aducanumab meaningfully slowed disease progression in participants with early AD."

Journal • P3 data • Alzheimer's Disease • CNS Disorders • APOE

Alzheimer's and Dementia Research Coverage in News Media Outlets Consumed by Population Groups that Are Underrepresented on Alzheimer's and Dementia-Focused Research Registries. (PubMed, Res Aging) - "The timeframe included the months before and after the US FDA's approval of the drug Aduhelm and the controversy surrounding it. Results highlight differences in under-represented groups' media consumption patterns and coverage of AD/dementia and indicates a failure to inform about an event that may have widespread effect on Medicare and AD/dementia research."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Comparison of safety of lecanemab and aducanumab: a real-world disproportionality analysis using the FDA adverse event reporting system. (PubMed, Front Pharmacol) - "This study identified some new PT signals and some PT signals showed gender differences. The median time-to-onset of ADEs due to lecanemab is shorter than that due to aducanumab."

Adverse events • Journal • Real-world evidence • Alzheimer's Disease • CNS Disorders

Antiamyloid treatment for dementia: concerns outweigh hopes. (PubMed, Curr Opin Psychiatry) - "It is still uncertain about the place of MABs in the treatment of Alzheimer's dementia. Further research is required regarding the long-term benefits and risks."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • TARDBP

Anti-amyloid antibody equilibrium binding to Aβ aggregates from human Alzheimer disease brain. (PubMed, bioRxiv) - "Equilibrium binding constants (K D ) and total Aβ binding (B max ) of recombinant aducanumab, lecanemab, and donanemab equivalents to human brain soluble and insoluble amyloid plaque-enriched and CAA-enriched Aβ aggregates. The APOE ε4 allele may plausibly increase ARIA-E risk by making antibody-accessible Aβ more soluble. These results have implications for improving the safety and efficacy of current and future anti-amyloid antibody therapies."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • APOE

Chimeric antigen receptors discriminate between tau and distinct amyloid-beta species. (PubMed, J Transl Med) - "Our findings demonstrate that CARs can detect and discriminate between tau PFFs, Aβ1-42, and Aβp3-42 aggregates. This highlights the potential of repurposing AD antibodies for CAR-based therapies to selectively target tau NFTs and distinct forms of Aβ senile plaques."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • Oncology • CD4 • CD69 • IL2RA

Prospects for treating Alzheimer's disease (PubMed, Zh Nevrol Psikhiatr Im S S Korsakova) - "Currently, the treatment of Alzheimer's disease (AD) is limited to symptomatic therapy with acetylcholinesterase inhibitors and memantine, which contribute to a temporary improvement in cognitive functions and increased independence in everyday life but have little effect on the progression rate of the neurodegenerative process...Anti-amyloid therapies such as aducanumab, lecanumab, and donanemab have recently been officially approved for practical use in some countries around the world. Therapeutic strategies for tau protein-related disorders, neuroinflammation, insulin resistance, and other neurodegeneration mechanisms are also being actively studied. Along with drug therapy, noninvasive brain stimulation methods such as transcranial magnetic stimulation and transcranial electrical stimulation, which have a high safety profile and proven effectiveness, are actively developing."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Developmental Disorders • Gene Therapies • Inflammation • Metabolic Disorders

Anti-amyloid immunotherapies for Alzheimer's disease: Administration, side effects, and overall framework. (PubMed, Geriatr Nurs) - "Recently, the Food and Drug Administration (FDA) approved the use of aducanumab (Aduhelm), lecanemab (Leqembi), and donanemab (Kisunla) in patients with mild cognitive impairment (MCI) and early-stage dementia secondary to Alzheimer's disease (AD). Given the novelty of these medications, limited educational resources are available to front line medical staff, primarily nurses, who are involved with patient education, administration of medications, and monitoring for side effects. The aim of this manuscript is to discuss the mechanism of action, indications, administration, and side effects associated with anti-amyloid immunotherapies and to provide medical staff with an assessment and educational framework to use in their practice."

Adverse events • Journal • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Cognitive Disorders • Dementia • Hematological Disorders