Aduhelm (aducanumab) / Neurimmune, Eisai - LARVOL DELTA

Aggregation-dependent epitope sequence and modification fingerprints of anti-Aβ antibodies. (PubMed, Elife) - "The monoclonal antibodies Aducanumab, Lecanemab, and Donanemab have recently been approved as the first disease-modifying treatments for early AD, highlighting the clinical importance of their exact binding profiles. Together, this work provides the most comprehensive dataset to date on aggregation-dependent sequence and modification selectivity of Aβ-Abs. By integrating mutational, PTM, and aggregation contexts in a unified experimental framework, we establish a resource that enables rational selection of antibodies for research and diagnostic applications and offers mechanistic insights that may inform the design and optimization of future therapeutic antibodies in AD."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Sex differences in efficacy/safety of anti-amyloid-beta monoclonal antibodies for the treatment of Alzheimer's disease. (PubMed, Transl Clin Pharmacol) - "With the recent approval of anti-amyloid-beta monoclonal antibodies-aducanumab, lecanemab, and donanemab-understanding sex differences in their clinical effects has become increasingly relevant. Potential mechanisms underlying these differences include sex-related variations in blood-brain barrier permeability, apolipoprotein E4-associated neuroinflammatory responses, and baseline disease characteristics. These findings underscore the need for future AD clinical trials to incorporate sex-based analyses and to consider sex as a key factor in optimizing treatment strategies."

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

FDA-Approved Passive Immunization Treatments Against Aβ in Alzheimer's Disease: Where Are We Now? (PubMed, Int J Mol Sci) - "This review covers the relationship between APOE4 status and the efficacy of FDA-approved monoclonal antibody (mAb) therapies, namely aducanumab, lecanemab, and donanemab. As it stands, high treatment costs, limited accessibility, and strict eligibility criteria all stand as barriers to treatment. By integrating the APOE4 genotype into treatment planning and focusing on disease-stage-specific approaches, a safer and more effective means of treating AD could be achieved."

FDA event • IO biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders

Differential conformational selections of three therapeutic antibodies binding to polymorphic Aβ oligomers. (PubMed, Int J Biol Macromol) - "Aducanumab shows polymorph-dependent binding, targeting N-terminal epitopes in full-length Aβ but maintaining non-specific contacts to cross-β structures. Lecanemab uniquely engages multiple N-termini simultaneously through an extended flat-binding interface. Donanemab employs a conserved CDRL1-dominated mode to recognize F4-H13 aggregates, with the pE3 modification acting as a structural anchor that reinforces binding stability. These structural insights provide a molecular basis for observed clinical outcomes and establish design principles for improved therapeutics targeting specific pathological aggregates."

Journal • Alzheimer's Disease • CNS Disorders

Nanobody Therapeutics in Alzheimer's Disease: From Molecular Mechanisms to Translational Approaches. (PubMed, Antibodies (Basel)) - "Comparison with FDA-approved anti-Aβ monoclonal antibodies (aducanumab, lecanemab, and donanemab) highlights opportunities and current translational gaps, including safety testing, half-life extension, and delivery optimization. This review critically delineates the current molecular mechanisms, emerging strategies, and delivery platforms, and emphasizes the potential of nanobodies as promising therapeutic and diagnostic molecules in AD therapeutics."

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

Treatment of animal models of Alzheimer's disease with extracellular vesicles or exosomes and involvement of microRNAs. (PubMed, Neural Regen Res) - "Conventional treatments focus on symptom management through acetylcholinesterase inhibitors, such as donepezil, galantamine, and rivastigmine, and the N-methyl-D-aspartate receptor antagonist memantine. However, the past few years have seen the approval of newer agents such as sodium oligomannate, aducanumab, and lecanemab, which show some promise in slowing disease progression...Loading extracellular vesicles and exosomes with microRNA mimics (e.g., miR-22, -29b, -124, -132, -138-5p, -342-5p, -711, and -7670-3p) or antagomirs (e.g., miR-206-antagomir) improved outcomes in animal models of Alzheimer's disease. Supporting results were found in the in vitro cell studies reviewed."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Inflammation • Vascular Neurology • MIR206 • MIR22

Analysis of the dual role of amyloid-beta in Alzheimer's disease through multi-omics integration. (PubMed, Neural Regen Res) - "Although monoclonal antibodies such as Aducanumab, Lecanemab, and Donanemab have been approved for marketing, their strict indications and high costs pose challenges for widespread promotion. In conclusion, this review suggests that amyloid-beta is not merely a pathological by-product but an environmentally responsive molecule with dual functions. A deeper understanding of the dynamic regulation of amyloid-beta, considering infection status and disease stage, can provide new directions for treatment strategies aimed at the prevention and treatment of Alzheimer's disease."

Journal • Alzheimer's Disease • CNS Disorders • Human Immunodeficiency Virus • Infectious Disease • Inflammation • APOE

The social construction of Aduhelm in the context of pharmaceutical ambiguity: exploring narratives from informal caregivers, medical professionals, and redditors on r/Alzheimers. (PubMed, Front Sociol) - "Drawing on sociological literature, we introduce the concept of pharmaceutical ambiguity, a theoretical framework for understanding these social phenomena. This study highlights how controversies like that surrounding Aduhelm can deeply erode trust in medical systems."

Journal • Alzheimer's Disease • CNS Disorders

DIFFERENTIAL INDUCTION OF ARIA-LIKE PATHOLOGIES BY ANTI-AΒ IMMUNOTHERAPIES IN 5XFAD MICE: A COMPREHENSIVE ANALYSIS OF 12-WEEKS DOSING WITH CLINICAL-STAGE ANTIBODIES (ADPD 2026) - " We treated 40-weeks-old 5XFAD mice (n=5-10 group) for 12 weeks with weekly (QW) intraperitoneal injections of: 1) Isotype-mIgG2 control, 2) 3D6-mIgG2 (murine precursor of bapineuzumab), 3) Aducanumab-mIgG2 (humanized), or 4) Remternetug-mIgG2 (humanized). This head-to-head study in a robust amyloidosis model demonstrates that the risk of inducing ARIA-like pathology is highly dependent on the specific antibody's properties. These preclinical findings provide critical mechanistic insights into ARIA pathogenesis and underscore the importance of antibody selection for mitigating treatment-emergent adverse events."

Preclinical • Alzheimer's Disease • Amyloidosis • CNS Disorders • Hematological Disorders • GFAP

PRECLINICAL AND CLINICAL STUDIES EXPLORING SCANNING ULTRASOUND FOR NEUROMODULATION AND DRUG DELIVERY IN ALZHEIMER'S DISEASE (ADPD 2026) - "In mice, we extended our published SUSonly and SUS+MB+Aducanumab/anti-tau-mAb findings by testing different methods to focally deliver vector drugs encoding proteins of various sizes. All study participants tolerated the SUSonly treatment, that was fast and safe, and with no drop-outs... The SUSonly safety trial met its primary and secondary endpoints in biomarker-confirmed mild-to-moderate AD. It informs our future work in an upcoming randomised controlled trial (RCT) in an AD population. Furthermore, our mouse studies present low-intensity ultrasound as an effective strategy for gene delivery to the brain, with implications beyond AD."

Preclinical • Alzheimer's Disease • CNS Disorders

EFFICACY AND SAFETY OF IMMUNOTHERAPIES FOR ALZHEIMER'S DISEASE: A NETWORK META-ANALYSIS (ADPD 2026) - "The results found that monoclonal antibodies such as aducanumab and solanezumab consistently ranked higher in terms of Surface Under the Cumulative Ranking (SUCRA) score. However, this contrasts with the outlier of shorter-term treatments as AN-1792 with QS-21, a vaccine, is found to be the better treatment option. For heightened comprehension on the efficacy and safety choice of immunotherapies, future wellconducted and designed large studies encompassing specific safety outcomes, financial analysis is highly recommended. Also, as monoclonal antibodies are seen as demonstrating a higher efficacy, it is imperative for more focus driven towards further increasing the safety of these specific types of immunotherapies in the future."

Retrospective data • Alzheimer's Disease • CNS Disorders

ACTIONS OF ANTI-AMYLOID-BETA ANTIBODIES AS OBSERVED BY HIGH-SPEED ATOMIC FORCE MICROSCOPY : THE COMPARISON OF ADUCANUMAB WITH LECANEMAB (ADPD 2026) - "Aducanumab has been approved by the FDA, and lecanemab and donanemab are on the market. Aducanumab bound to spherical and curvilinear oligomers (protofibrils) and to fibrils. However, the amount of aducanumab bound to protofibrils was significantly lower than the amount bound to lecanemab. In addition, consistent with previous study results, aducanumab binding to fibrils did not significantly inhibit fibril elongation."

Aβ42

SPATIAL DYNAMICS OF AMYLOID-ΒETA CLEARANCE IN ADUCANUMAB-TREATED ALZHEIMER'S DISEASE (ADPD 2026) - "Disproportionate Aβ clearance and ARIA-associated neuropathology localized to superficial cortical layers suggest a distinctive pattern of target engagement by aducanumab. These findings inform understanding and monitoring of similar Aβ-targeting therapies"

Alzheimer's Disease • CNS Disorders • APOE • Aβ42 • CD68

MULTI-OMIC CHARACTERIZATION OF BRAIN AND BIOFLUID RESPONSES TO ADUCANUMAB AND VERUBECESTAT IN AN AMYLOID MOUSE MODEL (ADPD 2026) - "These results showcase the utility of pharmacogenomic approaches in preclinical animal testing of candidate therapeutics, and highlight the broad and often adverse molecular consequences of candidate anti-amyloid treatments."

Preclinical • APOE

ENDOTHELIAL CELL-SPECIFIC EXPRESSION OF APP770 IN APP KNOCK-IN MICE EXACERBATES ARIA PATHOLOGY (ADPD 2026) - "Since we previously generated endothelial cell-specific APP770 transgenic mice (EC-APP770+) that exhibit prominent CAA pathology, we examined whether this model could serve as a useful tool to study ARIA. Twelve-month-old EC-APP770+:AppNL-G-F/wt mice and AppNL-G-F/wt littermates were treated with aducanumab (Aduhelm) once weekly for four weeks... Endothelial cell-specific expression of human APP770 in APP knock-in mice leads to exacerbation of ARIA pathology compared with conventional AD models. This novel mouse model may serve as a valuable tool for investigating ARIA mechanisms and for the preclinical evaluation of therapeutic strategies."

Preclinical • Alzheimer's Disease • CNS Disorders • Hematological Disorders • Inflammation

New Drug Therapies Against Targeting Neurodegenerative Diseases: A Comprehensive Review. (PubMed, Cent Nerv Syst Agents Med Chem) - "In Alzheimer's disease, specific antibodies targeting the β-amyloid protein (aducanumab, lecanemab, and others) are gaining special interest due to the approval of the first particular drugs against this disease...In amyotrophic lateral sclerosis, the appearance of newly approved drugs such as tofersen and edaravone, and some others in clinical Phase II (bosutinib), opens a new era in the understanding and treatment of this condition...In vascular dementia, numerous in vivo trials with molecules of different natures (flavonoids and lactones) have yielded positive results, delaying the progression of the disease. This review examines recent reports on molecules evaluated in vivo and in vitro models of the primary neurodegenerative diseases."

Journal • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Cognitive Disorders • Dementia • Frontotemporal Lobar Degeneration • Lewy Body Disease • Movement Disorders • Parkinson's Disease • Psychiatry • Schizophrenia

Biomarkers. (PubMed, Alzheimers Dement) - P1 | "The preliminary results suggest safety and feasibility of combining FUS-BBB opening with Lecanemab for targeted therapy in AD. The study highlights the potential of accelerated amyloid plaque clearance with combined FUS-BBBO and mAb. Additional studies with more patients and extended follow-up periods are warranted to validate these initial findings, aid in patient selection, optimized mAB and FUS-BBB doses, and evaluate the potential clinical benefits of this novel approach."

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

Biomarkers. (PubMed, Alzheimers Dement) - "We observed excellent target engagement, with piecewise regression models showing rates of Aβ clearance comparable to those seen in Phase 3 trials. The study was underpowered to detect cognitive benefits, which are limited over a short follow-up interval. These findings underscore the utility of observational studies with biomarker data in evaluating treatment efficacy, offering insights that complement traditional randomized trials."

Biomarker • Journal • Alzheimer's Disease • CNS Disorders • Dementia • APOE

Drug Development. (PubMed, Alzheimers Dement) - "Using epidemiologic and econometric methods to analyze individual-level data from trials of amyloid-targeting drugs will improve our understanding of amyloid as a surrogate outcome for cognition. In this instance, results are imprecise because solanezumab did not effectively remove amyloid. However, reproducing these analyses using individual-level data from effective anti-amyloid trials has the potential to shape treatment strategies and inform use of surrogate outcomes in future approval processes."

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

Dementia Care Research and Psychosocial Factors. (PubMed, Alzheimers Dement) - "Our analysis of studies on mAb therapy for AD concluded that these new therapies significantly impact the reduction of amyloid plaques and the slowing of cognitive decline in the early stages of the disease. Nevertheless, these alternative interventions present new risks and still need to prove their clinical applicability in more robust studies, particularly regarding safety, infrastructure, and costs. Therefore, further research should aim to address these challenges in the fight against AD using mAbs."

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

Drug Development. (PubMed, Alzheimers Dement) - P2 | "Compared to the recombinant Aβ monoclonal antibody therapeutics tested, sabirnetug showed the highest selectivity for AβOs over monomeric Aβ. Sabirnetug's observed high level of selectivity makes it well positioned to target AβOs in MCI/AD tissues and biofluids."

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

Drug Development. (PubMed, Alzheimers Dement) - "All drugs showed a statistically significant difference ADAS-Cog scores relative to placebo. However, mAbs are tested and approved for Mild Cognitive Impairment (MCI) or mild dementia. On the other hand, AChEIs were tested and approved for moderate to severe AD. Since these studies employed different versions of the ADAS-Cog scale (e.g., ADAS-Cog 11 vs. ADAS-Cog 13), making direct comparisons of efficacy more difficult. Additional research is needed to fully assess the efficacy of these newer therapies compared to placebo."

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

Drug Development. (PubMed, Alzheimers Dement) - "Sex-dependent differential clearance of amyloid plaques with monoclonal antibody treatment has been observed translationally across species. The interaction with IgG may contribute to both the amyloid-lowering effects and possibly to the reported adverse events. Results from this study will inform future MODEL-AD PTC evaluations of novel therapeutics, particularly those combined with or following anti-Aβ immunotherapies once amyloid is lowered and the disease continues to progress, and importantly to identify and predict differential effects of sex."

Journal • Alzheimer's Disease • CNS Disorders

Drug Development. (PubMed, Alzheimers Dement) - "The Adufab-TAT-(GGGGS)₄ conjugate shows strong binding to the transferrin receptor, with potential for enhanced blood-brain barrier penetration. This strategy could improve Alzheimer's disease treatment. Future research should validate its effectiveness through experimental assays and in vivo models to confirm its therapeutic potential."

Journal • Alzheimer's Disease • CNS Disorders

Drug Development. (PubMed, Alzheimers Dement) - "Patients undergoing anti-amyloid therapy are at risk of developing ARIAs, particularly those carrying the ApoE4 genotype. ARIAs are generally asymptomatic, do not necessitate treatment discontinuation, and show differing courses depending on the subtype: ARIA-E resolves spontaneously, while ARIA-H persists. Aducanumab was associated with the highest frequency of ARIA events. These findings underscore the importance of regular MRI monitoring and patient-specific management strategies to mitigate complications and optimize therapy outcomes."

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