ArticleProceedings of the National Academy of Sciences of the United States of America2021
Homocysteine fibrillar assemblies display cross-talk with Alzheimer's disease β-amyloid polypeptide.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 49 citations in OpenAlex.
- Shikimate pathway disruption in yeast induces metabolite self-assembly into toxic aggregates.The FEBS journal · 2026Article
- Review
- Homocysteine levels do not impact cognitive profile in frontotemporal dementia.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Allopurinol Reprograms Uric Acid Self-Assembly by Disrupting Cytotoxic Fibrils and Redirecting Crystal Growth.JACS Au · 2025Article
- Article
- Association and interaction of blood homocysteine and p-tau217 levels with temporal cortical thinning and cognitive impairment in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Diagnostic dynamic contrast-enhanced magnetic resonance imaging blood-brain barrier assessment combined with plasma biomarkers for mild cognitive impairment.World journal of psychiatry · 2025Article
- Correlations of cognitive function with serum levels of homocysteine, sex hormone binding globulin, and leptin in patients with schizophrenia.Pakistan journal of medical sciences · 2024Article
- Development of a chemiluminescent immunoassay based on magnetic solid phase for quantification of homocysteine in human serum.BMC biotechnology · 2024Article
- Article
- Branched-Chain Amino Acid Assembly into Amyloid-like Fibrils Provides a New Paradigm for Maple Syrup Urine Disease Pathology.International journal of molecular sciences · 2023Article
- Cdk12 maintains the integrity of adult axons by suppressing actin remodeling.Cell death discovery · 2023Article
- Realization of Amyloid-like Aggregation as a Common Cause for Pathogenesis in Diseases.Life (Basel, Switzerland) · 2023Review
- Small molecule metabolites: discovery of biomarkers and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer's disease and dementia: New evidence, potential therapeutic strategies, and biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- Diet's Role in Modifying Risk of Alzheimer's Disease: History and Present Understanding.Journal of Alzheimer's disease : JAD · 2023Review
- Rivastigmine Reverses the Decrease in Synapsin and Memory Caused by Homocysteine: Is There Relation to Inflammation?Molecular neurobiology · 2022Article
- Toxic Metabolites and Inborn Errors of Amino Acid Metabolism: What One Informs about the Other.Metabolites · 2022Review
- Functional amyloids from bacterial biofilms - structural properties and interaction partners.Chemical science · 2022Review
- Naturally Occurring Antioxidant Therapy in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High levels of homocysteine are reported as a risk factor for Alzheimer's disease (AD). Correspondingly, inborn hyperhomocysteinemia is associated with an increased predisposition to the development of dementia in later stages of life. Yet, the mechanistic link between homocysteine accumulation and the pathological neurodegenerative processes is still elusive. Furthermore, despite the clear association between protein aggregation and AD, attempts to develop therapy that specifically targets this process have not been successful. It is envisioned that the failure in the development of efficacious therapeutic intervention may lie in the metabolomic state of affected individuals. We recently demonstrated the ability of metabolites to self-assemble and cross-seed the aggregation of pathological proteins, suggesting a role for metabolite structures in the initiation of neurodegenerative diseases. Here, we provide a report of homocysteine crystal structure and self-assembly into amyloid-like toxic fibrils, their inhibition by polyphenols, and their ability to seed the aggregation of the AD-associated β-amyloid polypeptide. A yeast model of hyperhomocysteinemia indicates a toxic effect, correlated with increased intracellular amyloid staining that could be rescued by polyphenol treatment. Analysis of AD mouse model brain sections indicates the presence of homocysteine assemblies and the interplay between β-amyloid and homocysteine. This work implies a molecular basis for the association between homocysteine accumulation and AD pathology, potentially leading to a paradigm shift in the understanding of AD initial pathological processes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.