Evidence map›Paper›PMID 40425446›Full record

ReviewThe journal of prevention of Alzheimer's disease2025

Bispecific brain-penetrant antibodies for treatment of Alzheimer's disease.

Dag Sehlin, Greta Hultqvist, Wojciech Michno, Ximena Aguilar, Amelia D Dahlén, Enrica Cerilli, Nadja M Bucher, Sara Lopes van den Broek, Stina Syvänen

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in The journal of prevention of Alzheimer's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed.

  1. Antibody-Based Biologics for CNS Disorders.Antibodies (Basel, Switzerland) · 2026
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  18. Editorial: Brain-penetrant antibodies for Alzheimer's disease: The next generation?The journal of prevention of Alzheimer's disease · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Dag SehlinDepartment of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, Uppsala 751 85, Sweden.
Greta HultqvistDepartment of Pharmacy, Uppsala University, Uppsala, Sweden.
Wojciech MichnoDepartment of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, Uppsala 751 85, Sweden; Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Ximena AguilarDepartment of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, Uppsala 751 85, Sweden.
Amelia D DahlénDepartment of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, Uppsala 751 85, Sweden.
Enrica CerilliDepartment of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, Uppsala 751 85, Sweden.
Nadja M BucherDepartment of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, Uppsala 751 85, Sweden.
Sara Lopes van den BroekDepartment of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, Uppsala 751 85, Sweden.
Stina SyvänenDepartment of Public Health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, Uppsala 751 85, Sweden. Electronic address: stina.syvanen@uu.se.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The emerging class of bispecific antibodies represents a significant advancement in Alzheimer's disease (AD) immunotherapy by addressing the limited brain concentrations achieved with conventional monoclonal antibodies. The majority of bispecific antibodies developed for AD treatment utilize transferrin receptor (TfR1)-mediated transcytosis to enhance blood-brain barrier (BBB) penetration, resulting in higher and more uniform brain concentrations compared to conventional antibodies. This improved delivery has demonstrated superior efficacy in reducing brain amyloid-beta (Aβ) burden. Additionally, TfR1-mediated delivery may help mitigate adverse effects such as amyloid-related imaging abnormalities (ARIA). This is likely achieved by a reduction in antibody accumulation at vascular Aβ deposits, resulting from the combined effects of lower dosing and a different brain entry route when using bispecific antibodies. Besides targeting Aβ, bispecific antibodies have been engineered to address other key pathological features of AD, including tau pathology and neuroinflammatory targets, which are critical drivers of disease progression. These antibodies also show promise in diagnostic applications, particularly as radioligands for antibody-based positron emission tomography (immunoPET), leveraging their rapid brain delivery and efficient and specific target engagement. Moreover, the principles of bispecific antibody technology have been adapted for use beyond immunotherapy. The incorporation of TfR1-binding domains into enzymes, antisense oligonucleotides, or viral vectors such as adeno-associated viruses broadens their therapeutic potential. These approaches may enable more efficient treatment strategies, not only for AD but also for other neurological disorders, by facilitating the delivery of diverse therapeutic agents across the BBB.

Indexed as

Alzheimer DiseaseAntibodies, BispecificBrainAmyloid beta-PeptidesAnimalsBlood-Brain BarrierHumansImmunotherapyReceptors, TransferrinAmyloid beta-PeptidesAntibodies, BispecificReceptors, TransferrinAlzheimer’s diseaseBispecific antibodyImmunotherapyThe blood-brain barrier

Identifiers

PMID40425446
PMCPMC12413732

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.