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Article
Open AccessSynthesis and evaluation of fluorine-18 labelled tetrazines as pre-targeting imaging agents for PET
The brain is a challenging target for antibody-based positron emission tomography (immunoPET) imaging due to the restricted access of antibody-based ligands through the blood–brain barrier (BBB). To overcome t...
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Article
Open AccessAltered amyloid-β structure markedly reduces gliosis in the brain of mice harboring the Uppsala APP deletion
Deposition of amyloid beta (Aβ) into plaques is a major hallmark of Alzheimer’s disease (AD). Different amyloid precursor protein (APP) mutations cause early-onset AD by altering the production or aggregation pro...
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Article
Open AccessCryo-EM of Aβ fibrils from mouse models find tg-APPArcSwe fibrils resemble those found in patients with sporadic Alzheimer’s disease
The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer’s disease. However, the properties of Aβ in such...
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Article
Open AccessAge, dose, and binding to TfR on blood cells influence brain delivery of a TfR-transported antibody
Transferrin receptor 1 (TfR1) mediated brain delivery of antibodies could become important for increasing the efficacy of emerging immunotherapies in Alzheimer's disease (AD). However, age, dose, binding to Tf...
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Article
Open AccessLong-term effects of immunotherapy with a brain penetrating Aβ antibody in a mouse model of Alzheimer’s disease
Brain-directed immunotherapy is a promising strategy to target amyloid-β (Aβ) deposits in Alzheimer’s disease (AD). In the present study, we compared the therapeutic efficacy of the Aβ protofibril targeting an...
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Article
Open AccessImmunoPET imaging of amyloid-beta in a rat model of Alzheimer’s disease with a bispecific, brain-penetrating fusion protein
Hijacking the transferrin receptor (TfR) is an effective strategy to transport amyloid-beta (Aβ) immuno-positron emission tomography (immunoPET) ligands across the blood–brain barrier (BBB). Such ligands are m...
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Article
Open AccessBrain pharmacokinetics of mono- and bispecific amyloid-β antibodies in wild-type and Alzheimer’s disease mice measured by high cut-off microdialysis
Treatment with amyloid-β (Aβ) targeting antibodies is a promising approach to remove Aβ brain pathology in Alzheimer's disease (AD) and possibly even slow down or stop progression of the disease. One of the ma...
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Article
Open AccessBlood–brain barrier penetrating neprilysin degrades monomeric amyloid-beta in a mouse model of Alzheimer’s disease
Aggregation of the amyloid-β (Aβ) peptide in the brain is one of the key pathological events in Alzheimer’s disease (AD). Reducing Aβ levels in the brain by enhancing its degradation is one possible strategy t...
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Article
Open AccessA Brain-Targeting Bispecific-Multivalent Antibody Clears Soluble Amyloid-Beta Aggregates in Alzheimer’s Disease Mice
Amyloid-β (Aβ) oligomers and protofibrils are suggested to be the most neurotoxic Aβ species in Alzheimer’s disease (AD). Hence, antibodies with strong and selective binding to these soluble Aβ aggregates are ...
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Article
Open AccessPET Imaging in Preclinical Anti-Aβ Drug Development
Positron emission tomography (PET), a medical imaging technique allowing for studies of the living human brain, has gained an important role in clinical trials of novel drugs against Alzheimer’s disease (AD). ...
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Article
Open AccessTransferrin Receptor Binding BBB-Shuttle Facilitates Brain Delivery of Anti-Aβ-Affibodies
Affibodies targeting amyloid-beta (Aβ) could potentially be used as therapeutic and diagnostic agents in Alzheimer’s disease (AD). Affibodies display suitable characteristics for imaging applications such as h...
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Article
Open AccessPinpointing Brain TREM2 Levels in Two Mouse Models of Alzheimer’s Disease
The triggering receptor expressed on myeloid cells 2 (TREM2) is expressed by brain microglia. Microglial activation, as observed in Alzheimer’s disease (AD) as well as in transgenic mice expressing human amylo...
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Article
Open AccessNovel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta
Amyloid-β (Aβ) immunotherapy is a promising therapeutic strategy in the fight against Alzheimer’s disease (AD). A number of monoclonal antibodies have entered clinical trials for AD. Some of them have failed d...
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Article
Open AccessBrain pharmacokinetics of two BBB penetrating bispecific antibodies of different size
Transferrin receptor (TfR1) mediated enhanced brain delivery of antibodies have been studied extensively in preclinical settings. However, the brain pharmacokinetics, i.e. brain entry, distribution and elimina...
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Article
Open AccessExtracellular vesicles from amyloid-β exposed cell cultures induce severe dysfunction in cortical neurons
Alzheimer’s disease (AD) is characterized by a substantial loss of neurons and synapses throughout the brain. The exact mechanism behind the neurodegeneration is still unclear, but recent data suggests that sp...
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Article
Open AccessSPECT imaging of distribution and retention of a brain-penetrating bispecific amyloid-β antibody in a mouse model of Alzheimer’s disease
Alzheimer’s disease (AD) immunotherapy with antibodies targeting amyloid-β (Aβ) has been extensively explored in clinical trials. The aim of this study was to study the long-term brain distribution of two radi...
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Article
Open AccessEngineered antibodies: new possibilities for brain PET?
Almost 50 million people worldwide are affected by Alzheimer’s disease (AD), the most common neurodegenerative disorder. Development of disease-modifying therapies would benefit from reliable, non-invasive pos...
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Article
Open AccessHeterogeneous drug tissue binding in brain regions of rats, Alzheimer’s patients and controls: impact on translational drug development
For preclinical and clinical assessment of therapeutically relevant unbound, free, brain concentrations, the pharmacokinetic parameter fraction of unbound drug in brain (fu,brain) is commonly used to compensate t...
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Article
Open AccessSecretion and Uptake of α-Synuclein Via Extracellular Vesicles in Cultured Cells
In Parkinson’s disease and other Lewy body disorders, the propagation of pathology has been accredited to the spreading of extracellular α-synuclein (α-syn). Although the pathogenic mechanisms are not fully un...
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Article
Open AccessAstroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer’s Disease
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by amyloid-beta (Aβ) deposition, hyperphosphorylation of tau, and neuroinflammation. Astrocytes, the most abundant glial cell type in the ...
