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@INPROCEEDINGS{Rizzo:283058,
author = {Rizzo, Marianna and Teunissen, Charlotte E and Brosseron,
Frederic and Kuhs, Sandra and Kollmorgen, Gwendlyn and
Zetterberg, Henrik and Blennow, Kaj and Krüger, Rejko and
Fernandes, Sara B Gomes and Aarsland, Dag and Borejko, Olga
and Chokoshvili, Davit and van der Flier, Wiesje M and
Lemstra, Afina W and Tijms, Betty M and Petzold, Gabor C and
Spottke, Annika and Frisoni, Giovanni B and Brockmann,
Kathrin and Gasser, Thomas and Fladby, Tormod and
Wettergreen, Marianne and Jessen, Frank and Düzel, Emrah
and Höglinger, Günter U and Chevalier, Claire and
Krishnan, Rajaraman and Visser, Pieter Jelle and Vos,
Stephanie J B},
collaboration = {consortium, IMI EPND},
title = {{A}ssociations between {CSF} complement factors and
biomarkers of amyloid, tau, neurofilament light chain, and
α‐synuclein in {AD}, {DLB}, and {PD}},
journal = {Alzheimer's and dementia},
volume = {21},
number = {Suppl 2},
issn = {1552-5260},
reportid = {DZNE-2025-01465},
pages = {e104363},
year = {2025},
abstract = {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.},
month = {Jul},
date = {2025-07-27},
organization = {Alzheimer’s Association
International Conference, Toronto
(Canada), 27 Jul 2025 - 31 Jul 2025},
keywords = {Humans / Female / Male / Biomarkers: cerebrospinal fluid /
Alzheimer Disease: cerebrospinal fluid / Aged / Amyloid
beta-Peptides: cerebrospinal fluid / Parkinson Disease:
cerebrospinal fluid / tau Proteins: cerebrospinal fluid /
alpha-Synuclein: cerebrospinal fluid / Lewy Body Disease:
cerebrospinal fluid / Peptide Fragments: cerebrospinal fluid
/ Neurofilament Proteins: cerebrospinal fluid / Aged, 80 and
over / Middle Aged / Complement System Proteins:
cerebrospinal fluid / Biomarkers (NLM Chemicals) / Amyloid
beta-Peptides (NLM Chemicals) / tau Proteins (NLM Chemicals)
/ alpha-Synuclein (NLM Chemicals) / Peptide Fragments (NLM
Chemicals) / Neurofilament Proteins (NLM Chemicals) /
neurofilament protein L (NLM Chemicals) / amyloid
beta-protein (1-42) (NLM Chemicals) / Complement System
Proteins (NLM Chemicals)},
cin = {AG Heneka / AG Spottke / AG Petzold / AG Gasser / AG Jessen
/ AG Düzel / Clinical Research (Munich)},
ddc = {610},
cid = {I:(DE-2719)1011303 / I:(DE-2719)1011103 /
I:(DE-2719)1013020 / I:(DE-2719)1210000 / I:(DE-2719)1011102
/ I:(DE-2719)5000006 / I:(DE-2719)1111015},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)1 / PUB:(DE-HGF)16},
pubmed = {pmid:41453027},
pmc = {pmc:PMC12742826},
doi = {10.1002/alz70856_104363},
url = {https://pub.dzne.de/record/283058},
}