ArticleAlzheimer's research & therapy2022
Aβ42 oligomer-specific antibody ALZ-201 reduces the neurotoxicity of Alzheimer's disease brain extracts.
Article in Alzheimer's research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Safety, tolerability and immunogenicity of vaccine ALZ-101 in patients with early Alzheimer's disease: randomised, controlled trial.Alzheimer's research & therapy · 2026Trial
- Tuberostemonine ameliorates Alzheimer's disease pathology by suppression of the p38 MAPK signaling pathway.iScience · 2026Article
- Label-Free Detection of Cellular Aβ Accumulation and Mitochondrial Dysfunction in AD Cell Models via Raman Microscopy.Analytical chemistry · 2026Article
- Pathogenic landscape shaped by cerebral amyloid oligomers.Neural regeneration research · 2026Article
- Depletion of microglial compensation in glial network: Disease-associated response dynamics in the revised amyloid hypothesis.Neuroprotection (Chichester, England) · 2026Review
- Using Plasma Amyloid Beta Oligomer to Screen in Alzheimer's Disease: A Pilot Study.International journal of molecular sciences · 2026Article
- Icaritin ameliorates mitochondrial dysfunction and autophagy impairment in cellular models of Alzheimer's disease.Frontiers in aging neuroscience · 2026Article
- Active Immunization Targeting Amyloid β for the Treatment of Alzheimer's Disease.Neuro-degenerative diseases · 2025Review
- Microglial activation states and their implications for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025Review
- Nanomaterials in targeting amyloid-β oligomers: current advances and future directions for Alzheimer's disease diagnosis and therapy.Beilstein journal of nanotechnology · 2025Review
- Structures of Oligomeric States of Tau Protein, Amyloid-β, α-Synuclein and Prion Protein Implicated in Alzheimer's Disease, Parkinson's Disease and Prionopathies.International journal of molecular sciences · 2024Review
- Honokiol relieves hippocampal neuronal damage in Alzheimer's disease by activating the SIRT3-mediated mitochondrial autophagy.CNS neuroscience & therapeutics · 2024Article
- The AβFrontiers in cellular neuroscience · 2024Article
- Modulating the RAGE-Induced Inflammatory Response: Peptoids as RAGE Antagonists.Chembiochem : a European journal of chemical biology · 2023Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn Alzheimer's disease (AD), amyloid-β 1-42 (Aβ42) neurotoxicity stems mostly from its soluble oligomeric aggregates. Studies of such aggregates have been hampered by the lack of oligomer-specific research tools and their intrinsic instability and heterogeneity. Here, we developed a monoclonal antibody with a unique oligomer-specific binding profile (ALZ-201) using oligomer-stabilising technology. Subsequently, we assessed the etiological relevance of the Aβ targeted by ALZ-201 on physiologically derived, toxic Aβ using extracts from post-mortem brains of AD patients and controls in primary mouse neuron cultures.
methodsMice were immunised with stable oligomers derived from the Aβ42 peptide with A21C/A30C mutations (AβCC), and ALZ-201 was developed using hybridoma technology. Specificity for the oligomeric form of the Aβ42CC antigen and Aβ42 was confirmed using ELISA, and non-reactivity against plaques by immunohistochemistry (IHC). The antibody's potential for cross-protective activity against pathological Aβ was evaluated in brain tissue samples from 10 individuals confirmed as AD (n=7) and non-AD (n=3) with IHC staining for Aβ and phosphorylated tau (p-Tau) aggregates. Brain extracts were prepared and immunodepleted using the positive control 4G8 antibody, ALZ-201 or an isotype control to ALZ-201. Fractions were biochemically characterised, and toxicity assays were performed in primary mouse neuronal cultures using automated high-content microscopy.
resultsAD brain extracts proved to be more toxic than controls as demonstrated by neuronal loss and morphological determinants (e.g. synapse density and measures of neurite complexity). Immunodepletion using 4G8 reduced Aβ levels in both AD and control samples compared to ALZ-201 or the isotype control, which showed no significant difference. Importantly, despite the differential effect on the total Aβ content, the neuroprotective effects of 4G8 and ALZ-201 immunodepletion were similar, whereas the isotype control showed no effect.
conclusionsALZ-201 depletes a toxic species in post-mortem AD brain extracts causing a positive physiological and protective impact on the integrity and morphology of mouse neurons. Its unique specificity indicates that a low-abundant, soluble Aβ42 oligomer may account for much of the neurotoxicity in AD. This critical attribute identifies the potential of ALZ-201 as a novel drug candidate for achieving a true, clinical therapeutic effect in AD.
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