ArticleAlzheimer's research & therapy2024
Associations of cerebrospinal fluid complement proteins with Alzheimer's pathology, cognition, and brain structure in non-dementia elderly.
Article in Alzheimer's research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- Baseline cerebrospinal fluid complement balance is associated with longitudinal memory decline in relation to plasma p‑tau181 levels in mild cognitive impairment.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Review
- Systematic proteomic analysis of neuroimaging metrics identifies therapeutic targets for pituitary neuroendocrine.NPJ systems biology and applications · 2026Article
- Structural signature of plasma proteins classifies the status of Alzheimer's disease.Nature aging · 2026Article
- Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Primary Amoebic Meningoencephalitis caused by Complement C2 Deficiency.medRxiv : the preprint server for health sciences · 2026Article
- Proteomic biomarkers of cognitive function,medRxiv : the preprint server for health sciences · 2026Article
- Systemic complement factors in aging, Alzheimer's disease and other dementias: a longitudinal study over 10 years.Molecular neurodegeneration · 2026Article
- Global C3 lowering in adulthood protects against hippocampal dysfunction and cognitive impairment in aged mice.Research square · 2025Article
- Atlas of Proteomic signatures of brain structure and its links to brain disorders.Nature communications · 2025Article
- LC-MS/MS proteomics identifies plasma proteins related to cognition over 9-year follow-up.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Brain-penetrant complement inhibition mitigates neurodegeneration in an Alzheimer's disease mouse model.Brain : a journal of neurology · 2025Article
- Beneficial versus Detrimental Effects of Complement-Microglial Interactions in Alzheimer's Disease.Brain sciences · 2024Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCerebrospinal fluid (CSF) complement activation is a key part of neuroinflammation that occurs in the early stages of Alzheimer's disease (AD). However, the associations of CSF complement proteins with AD pathology, cognition, and structural neuroimaging biomarkers for AD have been rarely investigated.
methodsA total of 210 participants (125 mild cognitive impairment [MCI] patients and 85 normal controls) were included from Alzheimer's Disease Neuroimaging Initiative (ADNI) database who measured AD pathology, cognition, and neuroimaging at baseline and every 12 months. The mixed-effect linear models were utilized to investigate longitudinal associations of CSF complement proteins with AD pathology, cognition, and neuroimaging in cognitively normal (CN) and mild cognitive impairment (MCI) subjects. Causal mediation analyses were conducted to explore the potential mediators between CSF complement proteins and cognitive changes.
resultsWe found that the subjects with low CSF complement protein levels at baseline had worse outcomes in AD pathology, indicated by their lowest concentrations observed in A + and A + T + individuals. The reduced CSF complement proteins were associated with faster accumulation of tau among CN subjects and with cognitive decline and greater brain atrophy of specific regions among MCI subjects. Furthermore, mediation analyses showed that the effects of CSF complement proteins on cognitive performance were partially mediated by regional brain structures (mediation proportions range from 19.78 to 94.92%; p < 0.05).
conclusionsThis study demonstrated that CSF complement proteins were involved in the early progression of AD. Our results indicated that regional brain atrophy might be a plausible way to connect CSF complement protein levels and cognition.
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