ArticleActa neuropathologica communications2019
Soluble aggregates present in cerebrospinal fluid change in size and mechanism of toxicity during Alzheimer's disease progression.
Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61 citing papers in PubMed, 90 citations in OpenAlex.
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- Ultrasensitive Protein Aggregate Quantification Assays for Neurodegenerative Diseases on the Simoa Platform.Analytical chemistry · 2025Article
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- ASC specks as a single-molecule fluid biomarker of inflammation in neurodegenerative diseases.Nature communications · 2024Article
- Accelerated Alzheimer's Aβ-42 secondary nucleation chronologically visualized on fibril surfaces.Science advances · 2024Article
- Co-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer's disease.Nature communications · 2024Article
- Xenografted human microglia display diverse transcriptomic states in response to Alzheimer's disease-related amyloid-β pathology.Nature neuroscience · 2024Article
- Performance of SOBA-AD blood test in discriminating Alzheimer's disease patients from cognitively unimpaired controls in two independent cohorts.Scientific reports · 2024Article
- A Relationship between the Structures and Neurotoxic Effects of Aβ Oligomers Stabilized by Different Metal Ions.ACS chemical neuroscience · 2024Article
- Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases.Molecular neurodegeneration · 2024Review
- Amyloid-β aggregates activate peripheral monocytes in mild cognitive impairment.Nature communications · 2024Article
- Cerebral organoids with chromosome 21 trisomy secrete Alzheimer's disease-related soluble aggregates detectable by single-molecule-fluorescence and super-resolution microscopy.Molecular psychiatry · 2024Article
- A single-domain antibody detects and neutralises toxic AβAlzheimer's research & therapy · 2024Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
Soluble aggregates of amyloid-β (Aβ) have been associated with neuronal and synaptic loss in Alzheimer's disease (AD). However, despite significant recent progress, the mechanisms by which these aggregated species contribute to disease progression are not fully determined. As the analysis of human cerebrospinal fluid (CSF) provides an accessible window into the molecular changes associated with the disease progression, we characterised soluble aggregates present in CSF samples from individuals with AD, mild cognitive impairment (MCI) and healthy controls using a range of sensitive biophysical methods. We used super-resolution imaging and atomic force microscopy to characterise the size and structure of the aggregates present in CSF and correlate this with their ability to permeabilise lipid membranes and induce an inflammatory response. We found that these aggregates are extremely heterogeneous and exist in a range of sizes, varying both structurally and in their mechanisms of toxicity during the disease progression. A higher proportion of small aggregates of Aβ that can cause membrane permeabilization are found in MCI CSF; in established AD, a higher proportion of the aggregates were larger and more prone to elicit a pro-inflammatory response in glial cells, while there was no detectable change in aggregate concentration. These results show that large aggregates, some longer than 100 nm, are present in the CSF of AD patients and suggest that different neurotoxic mechanisms are prevalent at different stages of AD.
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