Biomarkers

Area of Science:

• Neuroscience
• Immunology
• Biochemistry

Background:

• The complement system's role in neurodegenerative diseases like Alzheimer's (AD), dementia with Lewy bodies (DLB), and Parkinson's (PD) is suggested but not fully understood.
• The association between complement factors and core disease biomarkers (amyloid, tau, NfL, α-synuclein) in cerebrospinal fluid (CSF) requires further investigation.

Purpose of the Study:

• To investigate the relationship between CSF complement factors and established biomarkers of neurodegeneration (amyloid-beta 42/40 ratio, phosphorylated tau 181, neurofilament light chain, and alpha-synuclein).
• To explore potential disease-specific associations of complement factors in AD, DLB, PD, and control groups.

Main Methods:

• Analysis of CSF samples from 321 participants (AD, DLB, PD, controls) from the EPND study.
• Quantification of CSF biomarkers (Aβ42/40, p-tau181, NfL, α-syn) and 14 complement factors.
• Linear regression models adjusted for age and sex, with post-hoc analysis based on Mini-Mental State Examination (MMSE) scores.

Main Results:

• Complement factors showed differential associations with biomarkers across diseases.
• Amyloid-beta 42/40 levels correlated with specific complement factors in controls and AD, but not DLB or PD.
• Phosphorylated tau 181, NfL, and α-synuclein exhibited broader associations with complement factors, with some disease-specific patterns observed for α-synuclein in PD.

Conclusions:

• CSF complement factors are associated with key neurodegenerative biomarkers, supporting the complement system's involvement in AD, DLB, and PD.
• Disease-specific relationships were identified between complement and amyloid in AD, and between complement and α-synuclein in PD.