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Updated: May 10, 2026
Quantitative 3D In Silico Modeling (q3DISM) of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
Published on: December 26, 2016
Specific uptake of an amyloid-β protofibril-binding antibody-tracer in AβPP transgenic mouse brain
Kristina Magnusson1, Dag Sehlin, Stina Syvänen
1Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden.
Abstract:
Evidence suggests that amyloid-β (Aβ) protofibrils/oligomers are pathogenic agents in Alzheimer's disease (AD). Unfortunately, techniques enabling quantitative estimates of these species in patients or patient samples are still rather limited. Here we describe the in vitro and ex vivo characteristics of a new antibody-based radioactive ligand, [125I]mAb158, which binds to Aβ protofibrils with high affinity. [125I]mAb158 was specifically taken up in brain of transgenic mice expressing amyloid-β protein precursor (AβPP) as shown ex vivo. This was in contrast to [125I]mAb-Ly128 which does not bind to Aβ. The uptake of intraperitoneally-administered [125I]mAb158 into the brain was age- and time-dependent, and saturable in AβPP transgenic mice with modest Aβ deposition. Brain uptake was also found in young AβPP transgenic mice that were devoid of Aβ deposits, suggesting that [125I]mAb158 targets soluble Aβ protofibrils. The radioligand was diffusely located in the parenchyma, sometimes around senile plaques and only occasionally colocalized with cerebral amyloid angiopathy. A refined iodine-124-labeled version of mAb158 with much improved blood-brain barrier passage and a shorter plasma half-life might be useful for PET imaging of Aβ protofibrils.
Insights
Researchers developed a new radioactive antibody, [125I]mAb158, that targets amyloid-beta (Aβ) protofibrils, key players in Alzheimer's disease (AD). This tracer shows promising brain uptake in mice, suggesting potential for diagnosing AD.
Area of Science:
- Neuroscience
- Radiochemistry
- Molecular Biology
Background:
- Amyloid-beta (Aβ) protofibrils/oligomers are implicated as pathogenic agents in Alzheimer's disease (AD).
- Current techniques for quantifying these species in patients or samples are limited.
- Development of specific diagnostic tools for AD is crucial.
Purpose of the Study:
- To characterize a novel antibody-based radioactive ligand, [125I]mAb158, for targeting Aβ protofibrils.
- To evaluate the in vitro and ex vivo properties of [125I]mAb158.
- To assess the potential of [125I]mAb158 for imaging Aβ protofibrils in the brain.
Main Methods:
- In vitro and ex vivo characterization of [125I]mAb158.
- Assessment of brain uptake in transgenic mice expressing amyloid-beta protein precursor (AβPP).
- Comparison with a non-binding control antibody ([125I]mAb-Ly128).
Main Results:
- [125I]mAb158 demonstrated high-affinity binding to Aβ protofibrils.
- Ex vivo studies showed specific uptake of [125I]mAb158 in the brains of AβPP transgenic mice.
- Brain uptake was age- and time-dependent, saturable, and observed even in mice without Aβ deposits, suggesting targeting of soluble Aβ protofibrils.
- The radioligand localized in the parenchyma, around plaques, and rarely with cerebral amyloid angiopathy.
Conclusions:
- [125I]mAb158 effectively targets Aβ protofibrils in vitro and ex vivo.
- The tracer shows potential for detecting soluble Aβ protofibrils in the brain.
- A modified version, [124I]mAb158, could be valuable for Positron Emission Tomography (PET) imaging in Alzheimer's disease diagnosis.
