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Associations of cerebrospinal fluid complement proteins with Alzheimer's pathology, cognition, and brain structure in non-dementia elderly

Cerebrospinal 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 inves...

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Published in:Alzheimer's research & therapy 2024-01, Vol.16 (1), p.12-12, Article 12
Main Authors: Li, Meng, Ma, Ya-Hui, Guo, Yun, Liu, Jia-Yao, Tan, Lan
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description Cerebrospinal 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. A 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. We 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 
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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 &lt; 0.05). This 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.</description><identifier>ISSN: 1758-9193</identifier><identifier>EISSN: 1758-9193</identifier><identifier>DOI: 10.1186/s13195-023-01377-5</identifier><identifier>PMID: 38238858</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Advertising executives ; Aged ; Alzheimer's disease ; Biomarkers ; Brain ; Brain structure ; Cerebrospinal fluid proteins ; Cognition ; Cognition &amp; reasoning ; Cognition disorders ; Complement ; Complement (Immunology) ; Dementia ; Development and progression ; Health aspects ; Magnetic resonance imaging ; Measurement ; Mediation ; Pathology ; Risk factors ; Size</subject><ispartof>Alzheimer's research &amp; therapy, 2024-01, Vol.16 (1), p.12-12, Article 12</ispartof><rights>2024. The Author(s).</rights><rights>COPYRIGHT 2024 BioMed Central Ltd.</rights><rights>2024. 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subjects Advertising executives
Aged
Alzheimer's disease
Biomarkers
Brain
Brain structure
Cerebrospinal fluid proteins
Cognition
Cognition & reasoning
Cognition disorders
Complement
Complement (Immunology)
Dementia
Development and progression
Health aspects
Magnetic resonance imaging
Measurement
Mediation
Pathology
Risk factors
Size
title Associations of cerebrospinal fluid complement proteins with Alzheimer's pathology, cognition, and brain structure in non-dementia elderly
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