ArticleAlzheimer's research & therapy2020
Targeting isoaspartate-modified Aβ rescues behavioral deficits in transgenic mice with Alzheimer's disease-like pathology.
Article in Alzheimer's research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Pooled it
- Peptide-based therapeutics in the management of Alzheimer's disease (AD) and their potential to develop novel strategies.Metabolic brain disease · 2026Review
- Multi-parametric longitudinal imaging of cerebral biomarkers in a rodent model of Alzheimer's disease.Photoacoustics · 2026Article
- Bridging prion biology and Alzheimer's disease: from pathogenic seeds to precision therapeutics.Frontiers in molecular neuroscience · 2025Review
- Identification of isoAsp7-Aβ as a major Aβ variant in Alzheimer's disease, dementia with Lewy bodies and vascular dementia.Acta neuropathologica · 2024Article
- Review
- The duality of amyloid-β: its role in normal and Alzheimer's disease states.Molecular brain · 2024Review
- Consequences of Amyloid-β Deficiency for the Liver.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Post-translational modifications of beta-amyloid modulate its effect on cell mechanical properties and influence cytoskeletal signaling cascades.Frontiers in molecular neuroscience · 2024Article
- Switching On/Off Amyloid Plaque Formation in Transgenic Animal Models of Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Zn-dependent β-amyloid Aggregation and its Reversal by the Tetrapeptide HAEE.Aging and disease · 2023Article
- Evidence for Enhanced Efficacy of Passive Immunotherapy against Beta-Amyloid in CD33-Negative 5xFAD Mice.Biomolecules · 2022Article
- The Dynamics of β-Amyloid Proteoforms Accumulation in the Brain of a 5xFAD Mouse Model of Alzheimer's Disease.International journal of molecular sciences · 2021Article
- First Immunoassay for Measuring Isoaspartate in Human Serum Albumin.Molecules (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAmyloid β (Aβ)-directed immunotherapy has shown promising results in preclinical and early clinical Alzheimer's disease (AD) trials, but successful translation to late clinics has failed so far. Compelling evidence suggests that post-translationally modified Aβ peptides might play a decisive role in onset and progression of AD and first clinical trials targeting such Aβ variants have been initiated. Modified Aβ represents a small fraction of deposited material in plaques compared to pan-Aβ epitopes, opening up pathways for tailored approaches of immunotherapy. Here, we generated the first monoclonal antibodies that recognize L-isoaspartate-modified Aβ (isoD7-Aβ) and tested a lead antibody molecule in 5xFAD mice.
methodsThis work comprises a combination of chemical and biochemical techniques as well as behavioral analyses. Aβ peptides, containing L-isoaspartate at position 7, were chemically synthesized and used for immunization of mice and antibody screening methods. Biochemical methods included anti-isoD7-Aβ monoclonal antibody characterization by surface plasmon resonance, immunohistochemical staining of human and transgenic mouse brain, and the development and application of isoD7-Aβ ELISA as well as different non-modified Aβ ELISA. For antibody treatment studies, 12 mg/kg anti-isoD7-Aβ antibody K11_IgG2a was applied intraperitoneally to 5xFAD mice for 38 weeks. Treatment controls implemented were IgG2a isotype as negative and 3D6_IgG2a, the parent molecule of bapineuzumab, as positive control antibodies. Behavioral studies included elevated plus maze, pole test, and Morris water maze.
resultsOur advanced antibody K11 showed a K
conclusionsThe present study demonstrates, for the first time, that the antibody-mediated targeting of isoD7-modified Aβ peptides leads to attenuation of AD-like amyloid pathology. In conjunction with previously published data on antibodies directed against pGlu-modified Aβ, the results highlight the crucial role of modified Aβ peptides in AD pathophysiology. Hence, the results also underscore the therapeutic potential of targeting modified amyloid species for defining tailored approaches in AD therapy.
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