ArticleTranslational neurodegeneration2022
N-terminally truncated Aβ4-x proteoforms and their relevance for Alzheimer's pathophysiology.
Article in Translational neurodegeneration, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
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- Post-Translational Modifications Distinguish Amyloid-β Isoforms in Cerebral Amyloid Angiopathy and Alzheimer's Disease.Journal of neurochemistry · 2025Article
- Antioxidants Trolox and Methazolamide Protect Microvascular Endothelial Cells from Oxidative Damage Induced by Sporadic and Familial Forms of Oligomeric Amyloid-β.Antioxidants (Basel, Switzerland) · 2025Article
- Combined Effects of Intermittent Hypoxia and Amyloid Beta on Hippocampal Activity, Its Cholinergic Modulation, and Memory.Hippocampus · 2025Article
- The Comorbidity of AD and PD: Exploring Clinical, Pathological, and Biomarker Interactions.Aging and disease · 2025Review
- Chemical imaging delineates Aβ plaque polymorphism across the Alzheimer's disease spectrum.Nature communications · 2025Article
- Functionally distinct pericyte subsets differently regulate amyloid-β deposition in patients with Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2025Article
- Identification of isoAsp7-Aβ as a major Aβ variant in Alzheimer's disease, dementia with Lewy bodies and vascular dementia.Acta neuropathologica · 2024Article
- Heterotypic Seeding Generates Mixed Amyloid Polymorphs.Small science · 2024Article
- Amyloid-β peptide signature associated with cerebral amyloid angiopathy in familial Alzheimer's disease with APPdup and Down syndrome.Acta neuropathologica · 2024Article
- Integrated Spatial Multi-Omics Study of Postmortem Brains of Alzheimer's Disease.Acta histochemica et cytochemica · 2024Article
- Heterotypic Seeding Generates Mixed Amyloid Polymorphs.bioRxiv : the preprint server for biology · 2024Article
- Cholinergic-like neurons and cerebral spheroids bearing the PSEN1 p.Ile416Thr variant mirror Alzheimer's disease neuropathology.Scientific reports · 2023Article
- Review
- Why the Ala-His-His Peptide Is an Appropriate Scaffold to Remove and Redox Silence Copper Ions from the Alzheimer's-Related Aβ Peptide.Biomolecules · 2022Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe molecular heterogeneity of Alzheimer's amyloid-β (Aβ) deposits extends well beyond the classic Aβ1-40/Aβ1-42 dichotomy, substantially expanded by multiple post-translational modifications that increase the proteome diversity. Numerous truncated fragments consistently populate the brain Aβ peptidome, and their homeostatic regulation and potential contribution to disease pathogenesis are largely unknown. Aβ4-x peptides have been reported as major components of plaque cores and the limited studies available indicate their relative abundance in Alzheimer's disease (AD).
methodsImmunohistochemistry was used to assess the topographic distribution of Aβ4-x species in well-characterized AD cases using custom-generated monoclonal antibody 18H6-specific for Aβ4-x species and blind for full-length Aβ1-40/Aβ1-42-in conjunction with thioflavin-S and antibodies recognizing Aβx-40 and Aβx-42 proteoforms. Circular dichroism, thioflavin-T binding, and electron microscopy evaluated the biophysical and aggregation/oligomerization properties of full-length and truncated synthetic homologues, whereas stereotaxic intracerebral injections of monomeric and oligomeric radiolabeled homologues in wild-type mice were used to evaluate their brain clearance characteristics.
resultsAll types of amyloid deposits contained the probed Aβ epitopes, albeit expressed in different proportions. Aβ4-x species showed preferential localization within thioflavin-S-positive cerebral amyloid angiopathy and cored plaques, strongly suggesting poor clearance characteristics and consistent with the reduced solubility and enhanced oligomerization of their synthetic homologues. In vivo clearance studies demonstrated a fast brain efflux of N-terminally truncated and full-length monomeric forms whereas their oligomeric counterparts-particularly of Aβ4-40 and Aβ4-42-consistently exhibited enhanced brain retention.
conclusionsThe persistence of aggregation-prone Aβ4-x proteoforms likely contributes to the process of amyloid formation, self-perpetuating the amyloidogenic loop and exacerbating amyloid-mediated pathogenic pathways.
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