Progression of Alzheimer's disease and effect of scFv‐h3D6 immunotherapy in the 3xTg‐AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy
Abstract
Alzheimer's disease (AD) is an incurable disease that affects most of the 47 million people estimated as living with dementia worldwide. The main histopathological hallmarks of AD are extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein. In recent years, Aβ-immunotherapy has been revealed as a potential tool in AD treatment. One strategy consists of using single-chain variable fragments (scFvs), which avoids the fragment crystallizable (Fc) effects that are supposed to trigger a microglial response, leading to microhemorrhages and vasogenic edemas, as evidenced in clinical trials with bapineuzumab. The scFv-h3D6 generated by our research group derives from this monoclonal antibody, which targets the N-terminal of the Aβ peptide and recognizes monomers, oligomers and fibrils. In this study, 3xTg-AD mice were intraperitoneally and monthly treated with 100 μg of scFv-h3D6 (a dose of ~3.3 mg/kg) or PBS, from 5 to 12 months of age (-mo), the age at which the mice were sacrificed and samples collected for histological and biochemical analyses. During treatments, four monitoring sessions using magnetic resonance imaging and spectroscopy (MRI/MRS) were performed at 5, 7, 9, and 12 months of age. MRI/MRS techniques are widely used in both human and mouse research, allowing to draw an in vivo picture of concrete aspects of the pathology in a non-invasive manner and allowing to monitor its development across ti…
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Sample sizes were not predetermined using statistical methods, but were similar to those reported in previous publications.
“Sample sizes were not predetermined using statistical methods; however, our sample sizes are similar to those reported in previous publications (Manno et al., 2019; Rollins et al., 2019; Güell-Bosch et al., 2020).”
From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Güell-Bosch et al., 2020
Another longitudinal study using the same mouse model found a significant decrease in the hippocampus, cerebellum, olfactory bulb, and cortex from 5 to 12 months.
“Another longitudinal study using the same mouse model found a significant decrease in the hippocampus, cerebellum, OLF and cortex from 5 to 12 months (Güell-Bosch et al., 2020).”
From Multimodal MRI combined with RNA sequencing reveals pathological signatures in the 9-month-old 3×Tg-AD mouse brain (2026) · cites this paper as Güell-Bosch et al., 2020
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- Authors
- Güell‐Bosch, J., Lope‐Piedrafita, S., Esquerda‐Canals, G., Montoliu‐Gaya, L., & Villegas, S.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Protein Design and Immunotherapy Group, Departament de Bioquímica i Biologia Molecular Facultat de Biociències, Universitat Autònoma de Barcelona Cerdanyola del Vallès, Barcelona Spain
- Corresponding author
- Lope‐Piedrafita, S.
- Villegas, S.
- Venue
- NMR in Biomedicine
- Publisher
- Wiley
- Published
- 2020-02-17
- Volume
- 33
- Issue
- 5
- Pages
- e4263-e4263
- ISSN
- 0952-3480 (ISSN-L)
- 1099-1492
- OpenAlex
- W3008557500
- Cited by
- 21
- References
- 8
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 3 · 2020: 2
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NMR in Biomedicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya (2014‐PROD00032)
- European Regional Development Fund
- Instituto de Salud Carlos III (FIS‐PI113‐01330)
- Ministerio de Economía y Competitividad (SAF2017‐89613R)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, scFv, 3xTg-AD mice, amyloid plaques, neurofibrillary tangles, brain volume, interleukin-6, microglial activation, longitudinal disease progression, intracerebroventricular administration
- MeSH terms
- Alzheimer Disease, Animals, Cerebral Cortex, Disease Models, Animal, Immunotherapy, Longitudinal Studies, Magnetic Resonance Imaging, Mice, Transgenic, Neurons, Magnetic Resonance Spectroscopy, Amyloid beta-Peptides, Disease Progression, Metabolomics, Single-Chain Antibodies, Plaque, Amyloid
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