TY  - CONF
AU  - Rizzo, Marianna
AU  - Teunissen, Charlotte E
AU  - Brosseron, Frederic
AU  - Kuhs, Sandra
AU  - Kollmorgen, Gwendlyn
AU  - Zetterberg, Henrik
AU  - Blennow, Kaj
AU  - Krüger, Rejko
AU  - Fernandes, Sara B Gomes
AU  - Aarsland, Dag
AU  - Borejko, Olga
AU  - Chokoshvili, Davit
AU  - van der Flier, Wiesje M
AU  - Lemstra, Afina W
AU  - Tijms, Betty M
AU  - Petzold, Gabor C
AU  - Spottke, Annika
AU  - Frisoni, Giovanni B
AU  - Brockmann, Kathrin
AU  - Gasser, Thomas
AU  - Fladby, Tormod
AU  - Wettergreen, Marianne
AU  - Jessen, Frank
AU  - Düzel, Emrah
AU  - Höglinger, Günter U
AU  - Chevalier, Claire
AU  - Krishnan, Rajaraman
AU  - Visser, Pieter Jelle
AU  - Vos, Stephanie J B
TI  - Associations between CSF complement factors and biomarkers of amyloid, tau, neurofilament light chain, and α‐synuclein in AD, DLB, and PD
JO  - Alzheimer's and dementia
VL  - 21
IS  - Suppl 2
SN  - 1552-5260
M1  - DZNE-2025-01465
SP  - e104363
PY  - 2025
AB  - While evidence suggests complement system involvement in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease (PD), its association with disease biomarkers remains unclear. We investigated the relationship of complement factors with amyloid, tau, NfL, and α-synuclein in CSF in AD, DLB, PD, and controls.We included 321 individuals with AD, DLB, PD, and controls from 6 centers of the EPND study. CSF Aβ42/40, p-tau181, NfL, and α-syn were centrally measured using NeuroToolKit (Roche Diagnostics), and 14 CSF complement factors using Milliplex (Merck KGaA). Controls were defined as normal cognition and normal Aβ42/40, whereas AD as abnormal Aβ42/40 without meeting clinical criteria of DLB or PD. Linear regression models adjusted for age and sex were used. Associations were post-hoc compared between individuals with low(≤23), intermediate(24-27), and high(≥28) MMSE scores.Sample characteristics are presented in Table 1. Lower Aβ42/40 levels were associated with lower levels of 7 complement factors in controls and with higher C1q and C2 levels specifically in AD (Figure 1, Figure 2). No associations of Aβ42/40 with complement were found in DLB and PD. Higher p-tau181 levels were associated with increased levels of 7 complement factors in controls and 6 in AD, and showed fewer associations in DLB and PD. The strength of p-tau181 associations with complement was similar across groups. Higher NfL levels were widely associated with higher complement factor levels in controls (13) and AD (12), and less in PD (6) and DLB (4). Higher α-syn levels were broadly associated with higher complement factor levels in AD (13), controls (12), and DLB (12), but only minimally in PD (1). The strength of these NfL and α-syn associations with complement was not disease-specific. Conversely, compared to all groups, in PD higher α-syn levels were associated with lower C5, C5a, C9, factor-I and properdin levels. Individuals with intermediate MMSE scores largely drove the associations of α-syn with complement in AD. MMSE level did not clearly impact other associations.CSF complement factors were associated with amyloid, tau, NfL, and α-synuclein, suggesting complement system involvement in several neurodegenerative diseases. Complement showed disease-specific associations with amyloid in AD and α-synuclein in PD.
T2  - Alzheimer’s Association International Conference
CY  - 27 Jul 2025 - 31 Jul 2025, Toronto (Canada)
Y2  - 27 Jul 2025 - 31 Jul 2025
M2  - Toronto, Canada
KW  - Humans
KW  - Female
KW  - Male
KW  - Biomarkers: cerebrospinal fluid
KW  - Alzheimer Disease: cerebrospinal fluid
KW  - Aged
KW  - Amyloid beta-Peptides: cerebrospinal fluid
KW  - Parkinson Disease: cerebrospinal fluid
KW  - tau Proteins: cerebrospinal fluid
KW  - alpha-Synuclein: cerebrospinal fluid
KW  - Lewy Body Disease: cerebrospinal fluid
KW  - Peptide Fragments: cerebrospinal fluid
KW  - Neurofilament Proteins: cerebrospinal fluid
KW  - Aged, 80 and over
KW  - Middle Aged
KW  - Complement System Proteins: cerebrospinal fluid
KW  - Biomarkers (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - alpha-Synuclein (NLM Chemicals)
KW  - Peptide Fragments (NLM Chemicals)
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - neurofilament protein L (NLM Chemicals)
KW  - amyloid beta-protein (1-42) (NLM Chemicals)
KW  - Complement System Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)1 ; PUB:(DE-HGF)16
C6  - pmid:41453027
C2  - pmc:PMC12742826
DO  - DOI:10.1002/alz70856_104363
UR  - https://pub.dzne.de/record/283058
ER  -