Aduhelm (aducanumab) / Neurimmune, Eisai - LARVOL DELTA

Antiamyloid Antibody Effects on Aβ-42 Protein Aggregates Profiled Using Nanospectroscopy. (PubMed, Chem Biomed Imaging) - "Importantly, neither aducanumab nor lecanemab was observed to induce any surface adsorption-driven disassembly of Aβ-42 protofibrils or elongated mature fibrils. Thus, nanospectroscopy enables direct characterization of antibody-amyloid interfacial interactions and provides insights into the distinct modes of action of emerging anti-Aβ therapeutics through label-free chemical imaging."

Journal • Alzheimer's Disease • CNS Disorders

Pharmacological and Clinical Heterogeneity of Anti-Amyloid Monoclonal Antibodies in Early Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Trials. (PubMed, Med Sci (Basel)) - "PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for phase III placebo-controlled trials evaluating lecanemab, donanemab, aducanumab, and gantenerumab in patients with mild cognitive impairment due to AD or mild AD dementia with biomarker confirmation of amyloid pathology. The benefit-risk profile appears heterogeneous across individual antibodies and may reflect pharmacological differences in amyloid targeting and clearance mechanisms. These findings support cautious, individualized use of anti-amyloid therapies and highlight the need for longer-term studies to determine whether short-term slowing of decline translates into clinically meaningful disease modification."

Biomarker • Clinical • Heterogeneity • Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Hematological Disorders

Landscape of Apolipoprotein (APOE) in the Emirati Population and Recommendations for a Genotyping Approach for Amyloid-Beta Monoclonal Antibodies (Aβ-mAbs) in Alzheimer's Disease Patients. (PubMed, Cureus) - "APOE profiling supports genotype-informed treatment strategies for anti-amyloid therapies. These findings establish a population-specific framework for integrating genetic information into the Emirati Genome Program pharmacogenomic report, enhancing precision medicine approaches for AD management in the UAE."

Journal • Alzheimer's Disease • CNS Disorders • APOE

Sustaining Drug Discovery Amid the Limits of Alzheimer's Disease Immunotherapies. (PubMed, eNeuro) - "Here, the critical barriers that limit the impact of anti-amyloid immunotherapies, including aducanumab, lecanemab, and donanemab, are discussed. Emerging evidence of accelerated brain atrophy and immunotherapy tolerance further complicates benefit-risk consultation. Sustaining drug- discovery pipelines by exploring combination therapies, tau-targeted approaches, drug repositioning, and novel small molecules through will be essential to provide comprehensive treatment options and personalized treatment plans for affected patients."

Journal • Review • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Dementia • Hematological Disorders • APOE

Comparative risk of amyloid-related imaging abnormalities with anti-amyloid-β monoclonal antibodies: A systematic review and penalized likelihood network meta-analysis of randomized trials. (PubMed, J Alzheimers Dis) - "The highest ARIA-E risk was seen with donanemab and aducanumab, followed by gantenerumab and lecanemab. APOE ε4 carriage significantly elevated ARIA-E (OR 2.28) and ARIA-H (OR 2.07) risk, with a clear gene-dose effect in homozygotes.ConclusionsARIA risk varies substantially across anti-amyloid-β therapies and is strongly modulated by APOE ε4 status. These findings support genotype-informed risk stratification and individualized MRI monitoring to optimize the benefit-risk balance of disease-modifying therapies in AD."

Journal • Retrospective data • Review • Alzheimer's Disease • CNS Disorders • Hematological Disorders • APOE

Anti-amyloid nanobody-Fc fusion protein drives potent amyloid clearance through microglial recruitment. (PubMed, Alzheimers Dement (N Y)) - "Our findings demonstrate that Fc effector function is indispensable for microglial-mediated amyloid clearance in vivo. By clarifying this fundamental mechanism, this study provides a framework for the rational design of next-generation immunotherapies. Furthermore, 2D10-Fc represents a promising therapeutic candidate, combining the high-affinity targeting of nanobodies with the effector power necessary for robust plaque clearance."

Journal • Alzheimer's Disease • CNS Disorders • APP

Clinicopathologic Evaluation of Amyloid Clearance in Alzheimer Disease. (PubMed, JAMA) - "To determine the postmortem and in vivo association between amyloid levels and downstream neuropathology after treatment with aducanumab in a patient with patchy areas showing minimal residual amyloid levels...In addition, amyloid clearance appears to preferentially occur in the gyral crests. Future studies should evaluate the differential mechanisms involved in amyloid clearance from superficial and deep cortical layers and in gyri and sulci because extensive amyloid clearance may be necessary to achieve downstream neuropathologic benefit after removal of amyloid."

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

Anti-amyloid immunotherapy drives APOE4 specific increases in glial reactivity, perivascular immune activation, and ARIA-like events. (PubMed, bioRxiv) - "9-month-old E2, E3, and E4FAD mice received weekly injections of chimeric Aducanumab (chAdu) or IgG control for 12 weeks, to assess APOE isoform-specific effects on amyloid dynamics, ARIA-H-like microhemorrhages, and underlying cellular and transcriptomic responses...Additionally, vascular branching analysis and parallel single cell and spatial transcriptomics revealed a loss of vascular plasticity and increased inflammatory and immune signaling in the neurovascular units of E4FAD mice. Together, these findings suggest the cerebrovasculature of E4s is uniquely susceptible to antibody mediated vascular damage and provide immunological targets for the assessment or mitigation of ARIA risk in this highest need population."

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

Predicting cognitive function in Alzheimer's clinical trials via amyloid β-protein biomarkers. (PubMed, Br J Clin Pharmacol) - "This study clarified the correlation and established predictive models for CDR-SB and ADAS-COG-11 based on amyloid imaging. This research identifies potential biomarkers and model-derived benchmarks for future dose selection and decision-making in Alzheimer's drug development, potentially accelerating the development of new treatments."

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

Molecular mechanisms underlying amyloid lowering by aducanumab: differential and comparative effects of sex and IgG reveal the post-treatment disease brain. (PubMed, bioRxiv) - "These findings demonstrate sex-dependent PK and pharmacodynamic responses to chAdu, identify biologically meaningful IgG-driven effects, and reveal molecular signatures that persist after amyloid reduction. This work provides biological insights into pathways that may remain insufficiently addressed following amyloid lowering; revealing novel targets for future drug discovery to prevent and treat disease."

Journal • Alzheimer's Disease • CNS Disorders • Aβ42

Regional Amyloid Clearance By Aducanumab Is Associated With Greater Cortical Preservation At Autopsy (AAIC 2026) - No abstract available

Biological Pathways Associated With Amyloid-related Imaging Abnormalities Following Aducanumab Treatment (AAIC 2026) - No abstract available

Apoe4 Drives Changes In Glial Reactivity After Aducanumab Immunotherapy (AAIC 2026) - No abstract available

Effects Of Aducanumab On Behavior And MRI Findings In EC-APP770+/AppNL-G-F Mice (AAIC 2026) - No abstract available

Preclinical

FDA Approval of Donanemab-azbt: A New Dawn in Alzheimer's Disease Treatment. (PubMed, Health Sci Rep) - "Acetylcholinesterase inhibitors (AChEIs) such as donepezil, galantamine, and rivastigmine are commonly used to enhance cognitive function by increasing acetylcholine levels, but they can cause side effects like nausea, bradycardia, and headaches. NMDA receptor antagonists, like memantine, reduce glutamatergic activity and are used to manage symptoms, yet are also associated with adverse effects including dizziness and agitation. Recently, monoclonal antibodies such as aducanumab have been developed to target amyloid-beta aggregates, though they are associated with amyloid-related imaging abnormalities (ARIA)...However, its use may result in ARIA and other adverse effects, necessitating careful clinical and radiological monitoring during treatment. Despite the risks of ARIA and other adverse events, Donanemab-azbt represents a promising addition to AD therapy, offering the potential for improved outcomes in patients with early symptomatic disease and expanding the..."

FDA event • Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Pain

Neuroinflammation-centered pathophysiology and therapeutic strategy design in Alzheimer's disease: Cutting-edge developments. (PubMed, Cell Signal) - "Recent FDA approvals of anti-amyloid monoclonal antibodies, including aducanumab and lecanemab, represent important advances toward disease-modifying therapy, although their long-term clinical impact and safety profiles remain under evaluation. This review synthesizes current understanding of AD pathogenesis through an inflammation-centered framework, highlighting clinically actionable immune pathways and stage-specific therapeutic windows. By integrating mechanistic insights with biomarker-driven strategies, we aim to delineate translational paths toward more precise, safe, and clinically meaningful disease modification."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • NLRP3

Neuropathological study of the effects of aducanumab anti-Aβ immunotherapy on patients with Alzheimer's disease. (PubMed, Acta Neuropathol) - "The selective reduction of neuritic, but not neurofibrillary tangle phospho-tau implies that Aβ-targeted antibodies such as aducanumab alleviate plaque-associated dystrophy but may not address established tangles. This study describes the long-term outcomes of anti-Aβ immunotherapy in AD."

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

Worth their weight in gray matter? A narrative review of cost-effectiveness analyses of monoclonal antibodies for Alzheimer's disease. (PubMed, Alzheimers Dement (N Y)) - "ICER variability across studies, despite reliance on the same clinical trials, reflects sensitivity to assumptions and potential sponsorship bias. Evidence is limited by small numbers of CEAs, reliance on modeled rather than real-world data, and absence of formal risk-of-bias scoring for individual CEAs. The cost-effectiveness of AD mAbs in the US context remains uncertain."

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

Dead-Space Microdomains as Explicit Barriers to Extracellular Drug Transport in Alzheimer's Disease. (PubMed, Pharm Res) - "The proposed framework provides a computationally efficient foundation for predictive multiphysics modeling in the human CNS and demonstrates how local ECS obstructions can lead to therapeutic hindrance in AD."

Journal • Alzheimer's Disease • CNS Disorders

Immunotherapeutic Innovations in Alzheimer's Disease: A Bibliometric Landscape of Global Research Trends and Evolution. (PubMed, Curr Neuropharmacol) - "Immunotherapy demonstrates disease-modifying potential in early-stage AD; however, it requires carefully optimized dosing regimens, precise biomarker-guided patient stratification, and integrated combinatorial strategies targeting Aβ, tau, and neuroinflammation. Future research should prioritize establishing robust translational models and promoting interdisciplinary collaboration to address preclinical-clinical translation gaps effectively."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • Immune Modulation • Immunology • Inflammation • NLRP3

Understanding quantitative effects of anti-amyloid therapies on tau biomarkers and functional outcome. Insights from a comprehensive mechanistic quantitative systems pharmacology study. (PubMed, Front Pharmacol) - "We derived an antibody specific normalized decrease of plasma p-tau181 (-15% for donanemab, -45% for aducanumab and -75% for lecanemab) to determine trial duration for achieving central amyloid negativity. This provides a hypothesis for the impact of disease pathology and gender effect on functional outcomes with lecanemab and gantenerumab. With further validation, this model has the capability to support optimization of clinical trial design for amyloid-tau combination therapy."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Dementia • p-tau181

In vitro comparison of Aβ-targeting SNIPR, synNotch, and TRUCK for cell-based drug delivery in Alzheimer's disease. (PubMed, bioRxiv) - "Here, we adapt these platforms to AD using a shared Aβ-targeting binding domain derived from Aducanumab (Aduhelm), coupled to inducible expression cassettes driving identical transgenes: secreted Metridia luciferase (MetLuc) and a Lecanemab (Leqembi)-based chimeric human-mouse antibody (chLecanemab). In contrast, both synNotch and SNIPR responded robustly to AβO, with SNIPR outperforming synNotch in both MetLuc and chLecanemab production. These findings establish SNIPR and synNotch as promising platforms for future research on cell-based targeted therapeutic delivery in AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cytomegalovirus Infection • Oncology • Targeted Protein Degradation • IL2 • NFATC1

Monoclonal antibodies and small molecules: on the cutting edge of Alzheimer's disease therapy. (PubMed, Front Cell Dev Biol) - "Recent anti-Aβ antibodies, such as aducanumab, lecanemab, and donanemab, have demonstrated significant biological activity and reductions in amyloid burden, leading to regulatory approvals that represent important proof-of-concept milestones. Their integration with emerging biomarkers, genetic profiling, and early diagnostic frameworks is driving a transition toward personalized and stage-specific treatment approaches. This review synthesizes current mechanistic insights, clinical evidence, and translational challenges of both modalities, highlighting how their convergence may shape the next-generation of AD therapeutics."

Journal • Review • Alzheimer's Disease • CNS Disorders

Real-world Clinical, Safety and Patient-reported Outcomes of Treatment with Lecanemab in a New England Alzheimer’s Disease Center (AAN 2026) - "Eight patients were initially on aducanumab and successfully transitioned to lecanemab. Of the survey responders, 93.5% (n=31, mean follow-up 298 days) reported feeling ‘very satisfied’ (20/31) or ‘satisfied’ (9/31) with lecanemab treatment and experiencing stabilization or slowing of disease progression on lecanemab. Conclusions Real-world evidence of lecanemab were consistent with published clinical trials, with no new safety signals and consistently positive patient-reported outcomes."

Clinical • Patient reported outcomes • Real-world • Real-world evidence • Alzheimer's Disease • CNS Disorders • Dementia

Presenter: Lifestyle Interventions vs. Monoclonal Antibodies in Mild Cognitive Impairment and Early Alzheimer’s Disease: A Comparative Review of Randomized Controlled Trials (AAN 2026) - "However, their relative clinical efficacy has not been systematically evaluated across trials using a common cognitive measure.Design/We reviewed randomized controlled trials (RCTs) through July 2025 that included either MMLIs or FDA-approved MABs (aducanumab, lecanemab, donanemab) and reported ADAS-Cog outcomes. MMLIs consistently improve cognition and confer broad health benefits, whereas MAB therapies robustly clear amyloid plaques but modestly preserve cognition. Future trials should directly compare and combine lifestyle and pharmacologic strategies. As with diabetes and cardiovascular disease, integrated treatment may provide the most effective approach for MCI and early AD."

Clinical • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Diabetes • Metabolic Disorders • Aβ42