pathway

COMPLEMENT

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about COMPLEMENT: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

3381Connections

30Hypotheses

0Analyses

50Outgoing

50Incoming

12Experiments

0Debates

Summary

COMPLEMENT is a biological pathway involved in neurodegeneration research. Key relationships include: activates, regulates, associated with. Associated with ALS, ALZHEIMER, ALZHEIMER'S. Connected to 1045 entities in the SciDEX knowledge graph.

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🔀 Pathway Info

Name	COMPLEMENT
Key Genes/Proteins	ABCA1, ABI3, ACE, ACETYL-COA, ACSL4, ACTB
Related Diseases	aging, Aging
Related Pathways	Adaptive Immunity

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

Complement System in Neurodegeneration

mechanism · 3221 words

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Pathway Diagram

graph TD
    COMPLEMENT["COMPLEMENT"] -->|"regulates"| SYNAPSE_ELIMINATION["SYNAPSE_ELIMINATION"]
    COMPLEMENT["COMPLEMENT"] -->|"activates"| Als["Als"]
    COMPLEMENT["COMPLEMENT"] -->|"activates"| Ms["Ms"]
    COMPLEMENT["COMPLEMENT"] -->|"interacts"| Als_1["Als"]
    COMPLEMENT["COMPLEMENT"] -->|"interacts"| Autism["Autism"]
    COMPLEMENT["COMPLEMENT"] -->|"therapeutic target"| Als_2["Als"]
    CEBPB["CEBPB"] -->|"regulates"| COMPLEMENT["COMPLEMENT"]
    NPTX2["NPTX2"] -->|"regulates"| COMPLEMENT["COMPLEMENT"]
    IGF2BP1["IGF2BP1"] -->|"interacts"| COMPLEMENT["COMPLEMENT"]
    ANK2["ANK2"] -->|"interacts"| COMPLEMENT["COMPLEMENT"]
    style COMPLEMENT fill:#1b5e20,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (1392)

Target	Relation	Type	Str
COMPLEMENT	encodes	protein	0.00
h-6b9dec7170	targeted_by	hypothesis	1.00
INFLAMMATION	activates	gene	1.00
Complement	regulates	pathway	1.00
Inflammation	activates	disease	1.00
Neuroinflammation	activates	disease	1.00
NEUROINFLAMMATION	activates	gene	1.00
Als	therapeutic_target	disease	1.00
Complement	therapeutic_target	pathway	1.00
Alzheimer	activates	disease	1.00
Neurodegeneration	activates	disease	1.00
Complement	inhibits	pathway	1.00
Aging	activates	disease	1.00
C1Q	activates	gene	1.00
Complement	activates	pathway	1.00
Complement	associated_with	pathway	1.00
ALZHEIMER	activates	gene	1.00
Inflammation	therapeutic_target	disease	1.00
Als	activates	disease	1.00
MICROGLIA	activates	gene	1.00
ASTROCYTES	activates	gene	1.00
AMYLOID	activates	gene	1.00
ALZHEIMER'S DISEASE	activates	gene	1.00
NEURON	activates	gene	1.00
MICROGLIA	therapeutic_target	gene	1.00
CYTOKINES	activates	gene	1.00
Phagocytosis	activates	pathway	1.00
Synaptic Pruning	mediates	process	0.95
Als	associated_with	disease	0.95
Synapse Loss	mediates	phenotype	0.95
Als	regulates	disease	0.95
Cancer	therapeutic_target	disease	0.95
Alzheimer's Disease	associated_with	disease	0.90
NEUROMYELITIS OPTICA SPECTRUM DISORDER	therapeutic_target	entity	0.90
Glaucoma	associated_with	disease	0.90
PHAGOCYTOSIS	activates	gene	0.90
Immune Response	regulates	pathway	0.90
Oxidative Stress	activates	pathway	0.90
MICROGLIA	regulates	gene	0.90
Alzheimer	inhibits	disease	0.85
Neurodegeneration	mediates	process	0.85
Inflammation	regulates	disease	0.85
Als	inhibits	disease	0.85
Neurodegeneration	therapeutic_target	disease	0.85
Neurodegeneration	regulates	disease	0.85
Alzheimer	associated_with	disease	0.85
Infection	activates	disease	0.85
Alzheimer	therapeutic_target	disease	0.85
Parkinson	activates	disease	0.85
ASTROCYTES	inhibits	gene	0.80

Incoming (1989)

Source	Relation	Type	Str
COMPLEMENT	encodes	gene	0.00
COMPLEMENT	therapeutic_target	gene	1.00
Als	therapeutic_target	disease	1.00
NEUROINFLAMMATION	activates	gene	1.00
COMPLEMENT	inhibits	gene	1.00
CYTOKINES	activates	gene	1.00
ALZHEIMER'S DISEASE	activates	gene	1.00
Inflammation	therapeutic_target	disease	1.00
NEURODEGENERATION	activates	gene	1.00
COMPLEMENT	regulates	gene	1.00
AMYLOID	activates	gene	1.00
Neurodegeneration	activates	disease	1.00
Neuroinflammation	activates	disease	1.00
Inflammation	activates	disease	1.00
ALZHEIMER	activates	gene	1.00
C1Q	activates	gene	1.00
Aging	activates	disease	1.00
Als	activates	disease	1.00
INFLAMMATION	activates	gene	1.00
Alzheimer	activates	disease	1.00
MICROGLIA	regulates	gene	1.00
COMPLEMENT	activates	gene	1.00
ASTROCYTES	activates	gene	1.00
Cancer	therapeutic_target	disease	1.00
CANCER	therapeutic_target	gene	1.00
INFLAMMATION	therapeutic_target	gene	1.00
Inflammation	regulates	disease	1.00
h-6b9dec7170	targets	hypothesis	1.00
MICROGLIA	activates	gene	1.00
COMPLEMENT	associated_with	gene	1.00
Als	regulates	disease	1.00
GENES	regulates	gene	1.00
Als	inhibits	disease	1.00
OXIDATIVE STRESS	activates	gene	1.00
MICROGLIA	therapeutic_target	gene	1.00
INFLAMMATION	regulates	gene	1.00
NEURODEGENERATION	activates	gene	1.00
NEURON	activates	gene	1.00
PHAGOCYTOSIS	activates	gene	1.00
Als	associated_with	disease	1.00
NEURODEGENERATION	regulates	gene	1.00
Early Metastatic Epithelial Cell Clusters	involved_in	cell_type	0.90
biomarkers-complement-c3	describes	wiki	0.90
ALZHEIMER'S DISEASE	therapeutic_target	gene	0.90
Neurodegeneration	regulates	disease	0.90
Alzheimer	regulates	disease	0.90
ALZHEIMER	regulates	gene	0.90
NEUROINFLAMMATION	therapeutic_target	gene	0.90
ASTROCYTE	activates	gene	0.90
ALZHEIMER	therapeutic_target	gene	0.90

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Complement Cascade Inhibition Synaptic Protection	0.867	neurodegeneration	View
Senescent Cell ASM-Complement Cascade Intervention	0.852	neurodegeneration	Lipid raft composition changes in synapt
Targeting SASP-Complement Amplification Through HIF-1α Downs	0.793	neurodegeneration	What molecular mechanism causes VCP muta
Differential Complement Regulator Expression on Synaptic Mem	0.783	synaptic biology	What determines the selectivity of compl
Complement C1q-Mediated Synaptic Pruning Drives Early Cognit	0.769	neurodegeneration	Legacy Pre-Pipeline Hypothesis Import

Selective blockade of classical-pathway activation downstrea	0.750	neurodegeneration	Does C1q function differ based on subcel
Complement-SASP Amplification Cascade as Mechanistic Link	0.741	neurodegeneration	Why have anti-Aβ clinical trials failed
Microglial TREM2-Complement Axis Modulation	0.726	neurodegeneration	Cell type vulnerability in Alzheimer's D
Excessive C1q/C3/CR3 complement cascade activation initiates	0.720	neurodegeneration	Synaptic pruning by microglia in neurode
SASP-Mediated Complement Cascade Amplification	0.700	neurodegeneration	Senolytic therapy for age-related neurod
Complement C1q Mimetic Decoy Therapy	0.695	neurodegeneration	Synaptic pruning by microglia in early A
Microglia and complement sustain post-Aβ neurodegeneration a	0.690	neurodegeneration	Does tau dendritic missorting persist in
Complement C1QA Spatial Gradient in Cortical Layers	0.678	Alzheimer's Disease	SEA-AD Gene Expression Profiling — Allen
Microglial TREM2 state determines whether C1q-tagged substra	0.670	neurodegeneration	Does C1q function differ based on subcel
LPS-primed microglial trained immunity establishes persisten	0.670	neurodegeneration	Synaptic pruning by microglia in neurode
Complement C1q Subtype Switching	0.665	neurodegeneration	4R-tau strain-specific spreading pattern
Complement C1QA Inhibition Synergizes with PV Interneuron Mo	0.659	neurodegeneration	What molecular mechanisms underlie the d
Astrocyte IL-1β as Paracrine Mediator of Microglial Compleme	0.658	neuroinflammation	How does sevoflurane-induced NF-κB activ
SUMO1-Mediated Synaptotagmin-1 SUMOylation at Lys124 Impairs	0.652	neurodegeneration	What are the specific PTM changes in syn
C1q has spatially distinct functions, with synapse-bound C1q	0.630	neurodegeneration	Does C1q function differ based on subcel
APOE4-microglial complement signaling causes cholinergic-enr	0.630	neurodegeneration	What determines the temporal sequence of
Tau fibrils expose neuronal phosphatidylserine and heat-shoc	0.620	neurodegeneration	Synaptic pruning by microglia in neurode
Complement Cascade Specificity: Microglial C3aR Antagonism D	0.618	synaptic biology	Does SPP1-mediated synaptic engulfment r
Complement-Mediated Synaptic Pruning Dysregulation	0.612	neurodegeneration	Gene expression changes in aging mouse b
H2: Perforant Path Synapse Loss via Early Complement Cascade	0.610	neurodegeneration	Entorhinal cortex layer II vulnerability
Female microglia exhibit heightened complement gene expressi	0.610	neurodegeneration	Synaptic pruning by microglia in neurode
TNF-α–C1r/C1s Bridge Between NF-κB and Classical Complement	0.600	neuroinflammation	How does sevoflurane-induced NF-κB activ
NAMPT-SIRT1 Axis as Master Regulator of SASP-Dependent Compl	0.592	neurodegeneration	test
TREM2-C1Q Competitive Binding to Prevent Complement-Mediated	0.591	neurodegeneration	Do β-amyloid plaques and neurofibrillary
H5: Complement Dysregulation Drives Synapse Loss via Senesce	0.580	neurodegeneration	Do APOE4-driven senescent astrocytes cau

Mentioning Analyses (0)

Scientific analyses that reference this entity

No analyses mention this entity

Experiments (12)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
Mobile App-Based Intervention for BPSD in Community-Dwelling Dementia	clinical	dementia with behavioral and p	0.950	0.00	human patients	proposed	N/A
Single-cell RNA sequencing analysis of human atherosclerotic plaques	exploratory	Atherosclerosis	0.900	0.00	Human atherosclerotic plaque s	proposed	N/A
Proposed experiment from debate on Synaptic pruning by microglia in ea	falsification	Alzheimer's Disease	0.400	0.50	mouse	proposed	$200,000
Proposed experiment from debate on Senolytics targeting p16/p21+ senes	falsification	Neurodegeneration	0.400	0.50	cell_line	proposed	$80,000
Biomechanical Impact Profiles and Chronic Traumatic Encephalopathy Phe	clinical	Neurodegeneration	0.400	0.50	in_silico	proposed	$180,000
Mechanism: Why Does Amyloid Removal Only Slow Decline 27%?	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$7,500,000
Experiment: Autoimmune Hypothesis Testing in AD	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
Experimental: CAAR-T Cell Therapy for Autoantibody-Mediated Neurotoxic	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000
cGAS-STING Pathway Validation Study in Parkinson's Disease	clinical	Parkinson's Disease	0.400	0.50	human	proposed	$7,100,000
Microglial Aging and Immune Memory in Neurodegeneration — Training the	validation	Alzheimer's Disease	0.400	0.50	human	proposed	$2,960,000
Microglial Contributions to Huntington's Disease Pathogenesis	validation	Neuroinflammation	0.400	0.50	human	proposed	$2,960,000
Mixed Pathology Effects on Parkinson's Disease Progression and Treatme	clinical	Alzheimer's Disease	0.400	0.50	human	proposed	$5,460,000

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Complement, Inflammasome, and Microglial Crosstalk in Glaucoma: From Neurodegene [PMID:41900887]	Chen TY, Wu N, Sun X	Life (Basel)	2026	1
Young adult microglial deletion of C1q reduces engulfment of synapses and preven [PMID:41000995]	Petrisko TJ, Chu SH, Gomez-Arboledas A,	bioRxiv : the preprint server	2025	1
Systemic Neurodegeneration and Brain Aging: Multi-Omics Disintegration, Proteost [PMID:40868276]	Voicu V, Toader C, Șerban M, Covache-Bus	Biomedicines	2025	1
Complement C1q/C3-CR3 signaling pathway mediates abnormal microglial phagocytosi [PMID:38642614]	Han QQ, Shen SY, Liang LF, Chen XR, Yu J	Brain Behav Immun	2024	1
Metabolic orchestration of cell death by AMPK-mediated phosphorylation of RIPK1. [PMID:37384704]	Zhang T, Xu D, Trefts E, Lv M, Inuzuka H	Science	2023	1
Microglia regulation of synaptic plasticity and learning and memory. [PMID:34472455]	Cornell J, Salinas S, Huang HY, Zhou M	Neural Regen Res	2022	1
The Role of Complement in Synaptic Pruning and Neurodegeneration. [PMID:34595138]	Gomez-Arboledas A, Acharya MM, Tenner AJ	ImmunoTargets and therapy	2021	1
Complement and microglia mediate early synapse loss in Alzheimer mouse models. [PMID:27033548]	Hong S, Beja-Glasser VF, Nfonoyim BM, Fr	Science	2016	1
Pioglitazone attenuates complement-mediated microglial synaptic engulfment in an [PMID:41396874]	Unknown	Brain : a journal of neurology	2026	0
Panacis Quinquefolii Radix Polysaccharides Alleviate Depressive-Like Behaviors i [PMID:41914021]	Xie M, Feng L, Li R, Li M, Shen L, Zhang	CNS neuroscience & therapeutic	2026	0
Vaccine-induced antibodies can limit Salmonella infection in the absence of comp [PMID:41738756]	Perez-Toledo M, Aksu-Istil K, Marcial-Ju	mBio	2026	0
The gain-of-function TREM2-T96K mutation increases risk for Alzheimer's disease [PMID:41109213]	Pilat DJ, Le H, Prokopenko D, Lin CJ, Ei	Neuron	2026	0
The Immuno-Glial Connectome in Alzheimer's Disease: Integrating Central and Peri [PMID:41569436]	Gopalakrishna PK, Che Mohd Nassir CMN, A	Cellular and molecular neurobi	2026	0
Messengers of coagulopathy: complement-carrying extracellular vesicles in SARS-C [PMID:41766448]	Taxiarchis A, Pruner I	Current opinion in hematology	2026	0
Alzheimer's Disease as a Disorder of Neuroimmune Dysregulation. [PMID:41745721]	Aranda-Abreu GE, Rojas-Durán F, Hernánde	Neurology international	2026	0
Microglia-neuron crosstalk in Alzheimer's disease: an exploration of molecular m [PMID:40651657]	Unknown	Neuroscience	2025	0
Age-related inflammatory changes and perineuronal net dynamics: implications for [PMID:41254697]	["Zachary A Colon", "Shannon C Chan", "K	Journal of neuroinflammation	2025	0
Cerebrospinal fluid β2-microglobulin promotes the tau pathology through mi [PMID:39748415]	["Zehu Sheng", "Lanyang Wang", "Ming Che	Alzheimer's research & the	2025	0
The cholesterol 24-hydroxylase CYP46A1 promotes α-synuclein pathology in Parkins [PMID:39964974]	Dai L, Wang J, Meng L, Zhang X, Xiao T,	PLoS biology	2025	0
PDE4 inhibition alleviates HMGB1/C1q/C3-mediated excessive phagocytic pruning of [PMID:39947489]	Zhao Q, Zeng C, Luo F, Xian Z, Wen H, Tu	Brain, behavior, and immunity	2025	0

Debates (0)

Multi-agent debates referencing this entity

No debates reference this entity

Related Research

Hypotheses and analyses mentioning COMPLEMENT in their description or question text

COMPLEMENT

Understanding Entity Pages

Summary

Wiki Pages (1)

Complement System in Neurodegeneration

Pathway Diagram

Outgoing (1392)

Incoming (1989)

Targeting Hypotheses (30)

Mentioning Analyses (0)

Experiments (12)

Related Papers (20)

Debates (0)

Related Research

Selective blockade of classical-pathway activation downstream of C1q will reduce

Complement-SASP Amplification Cascade as Mechanistic Link

Microglial TREM2-Complement Axis Modulation

Excessive C1q/C3/CR3 complement cascade activation initiates pre-symptomatic syn

SASP-Mediated Complement Cascade Amplification

Complement C1q Mimetic Decoy Therapy

Microglia and complement sustain post-Aβ neurodegeneration after tau missorting

Complement C1QA Spatial Gradient in Cortical Layers

Microglial TREM2 state determines whether C1q-tagged substrates are cleared adap

LPS-primed microglial trained immunity establishes persistent H3K4me3 landscapes

Complement C1q Subtype Switching

Complement C1QA Inhibition Synergizes with PV Interneuron Modulation

Astrocyte IL-1β as Paracrine Mediator of Microglial Complement Expression

SUMO1-Mediated Synaptotagmin-1 SUMOylation at Lys124 Impairs Calcium Sensing and

C1q has spatially distinct functions, with synapse-bound C1q primarily nucleatin