ArticleMolecular neurodegeneration2023
Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity.
Article in Molecular neurodegeneration, 2023. 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, 23 citations in OpenAlex.
- Article
- Orthogonal Ionic Liquid-Based Extraction Strategy Enables Amyloid-Specific Profiling of Aggregate Proteome.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Roles of RNA-Binding Nuclear Proteins in Alzheimer's Disease Pathophysiology.ACS pharmacology & translational science · 2026Review
- DNA methylation regulation of CYP450-lipid metabolism by high-altitude hypoxia: linking neuroinflammation to cognitive impairment.Journal of neuroinflammation · 2026Article
- Alzheimer's disease-linked ACE variants increase ACE1 catalytic activity and production of angiotensin II.The Journal of biological chemistry · 2026Article
- Levetiracetam prevents Aβ production through SV2a-dependent modulation of APP processing in Alzheimer's disease models.Science translational medicine · 2026Article
- Neuronal subtype governs amyloid structure, cellular response, and cognitive outcome in genetically targeted APP mouse models.Molecular neurodegeneration · 2026Article
- Harnessing copper: Innovative approaches to combat neurodegenerative diseases and cancer (Review).International journal of molecular medicine · 2026Review
- The diagnostic value of plasma Aβ42 and Aβ40 in Alzheimer's disease: current status, challenges, and impacting variables.Journal of neurology · 2025Review
- Isotope-encoded spatial biology identifies plaque-age-dependent maturation and synaptic loss in an Alzheimer's disease mouse model.Nature communications · 2025Article
- Unveiling the Interplay: Neurovascular Coupling, Astrocytes and G Protein-Coupled Receptors in Alzheimer's Disease.ACS pharmacology & translational science · 2025Review
- Amyloids in bladder cancer hijack cancer-related proteins and are positive correlated to tumor stage.Scientific reports · 2025Article
- Tangeretin offers neuroprotection against colchicine-induced memory impairment in Wistar rats by modulating the antioxidant milieu, inflammatory mediators and oxidative stress in the brain tissue.BMC complementary medicine and therapies · 2025Article
- Recent Insights on the Role of Nuclear Receptors in Alzheimer's Disease: Mechanisms and Therapeutic Application.International journal of molecular sciences · 2025Review
- Innovative applications and future perspectives of chromatography-mass spectrometry in drug research.Frontiers in pharmacology · 2025Review
- "Proteinjury": a universal pathological mechanism mediated by cerebrospinal fluid in neurodegeneration and trauma.Frontiers in cell and developmental biology · 2025Review
- Upregulation of Na/H Exchanger in Astrogliosis and Early Alzheimer's Disease Pathogenesis.Aging and disease · 2024Article
- Targeting Iron Responsive Elements (IREs) of APP mRNA into Novel Therapeutics to Control the Translation of Amyloid-β Precursor Protein in Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Sex Differences in Blood Accumulation of Neurodegenerative-Related Proteins and Antioxidant Responses to Regular Physical Exercise.Journal of molecular neuroscience : MN · 2024Article
- Physiopathological mechanisms underlying Alzheimer's disease: a narrative review.Dementia & neuropsychologia · 2024Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe accumulation of amyloid beta (Aβ) peptides in fibrils is prerequisite for Alzheimer's disease (AD). Our understanding of the proteins that promote Aβ fibril formation and mediate neurotoxicity has been limited due to technical challenges in isolating pure amyloid fibrils from brain extracts.
methodsTo investigate how amyloid fibrils form and cause neurotoxicity in AD brain, we developed a robust biochemical strategy. We benchmarked the success of our purifications using electron microscopy, amyloid dyes, and a large panel of Aβ immunoassays. Tandem mass-spectrometry based proteomic analysis workflows provided quantitative measures of the amyloid fibril proteome. These methods allowed us to compare amyloid fibril composition from human AD brains, three amyloid mouse models, transgenic Aβ42 flies, and Aβ42 seeded cultured neurons.
resultsAmyloid fibrils are primarily composed by Aβ42 and unexpectedly harbor Aβ38 but generally lack Aβ40 peptides. Multidimensional quantitative proteomics allowed us to redefine the fibril proteome by identifying 20 new amyloid-associated proteins. Notably, we confirmed 57 previously reported plaque-associated proteins. We validated a panel of these proteins as bona fide amyloid-interacting proteins using antibodies and orthogonal proteomic analysis. One metal-binding chaperone metallothionein-3 is tightly associated with amyloid fibrils and modulates fibril formation in vitro. Lastly, we used a transgenic Aβ42 fly model to test if knock down or over-expression of fibril-interacting gene homologues modifies neurotoxicity. Here, we could functionally validate 20 genes as modifiers of Aβ42 toxicity in vivo.
conclusionsThese discoveries and subsequent confirmation indicate that fibril-associated proteins play a key role in amyloid formation and AD pathology.
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Registered trials
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.