SciDEX — AD

disease

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about AD: 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.

1509Connections

30Hypotheses

30Analyses

50Outgoing

50Incoming

10Experiments

20Debates

Summary

AD is a disease characterized by neurodegeneration research. Key relationships include: implicated in, associated with, causes. Associated with DEMENTIA, T2D, T2DM. Connected to 236 entities in the SciDEX knowledge graph.

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Disease Info

Associated Genes	A2M, ABCA1, ABCB1, ABCD3, ABCG1, ACHE, ACTB, AGER
Therapeutic Agents	HTL9936, resveratrol
KG Connections	1498 knowledge graph edges
Databases	OMIM Orphanet ClinicalTrials PubMed

Wiki Pages (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    AD["AD"] -->|"causes"| neurodegeneration["neurodegeneration"]
    AD["AD"] -->|"causes"| memory_loss["memory_loss"]
    AD["AD"] -->|"associated"| TAU["TAU"]
    AD["AD"] -->|"causes"| IMMUNE_TOL["IMMUNE_TOL"]
    AD["AD"] -->|"causes"| DEMENTIA["DEMENTIA"]
    AD["AD"] -.->|"inhibits"| cholinergic_transmission["cholinergic_transmission"]
    TAU_1["TAU"] -->|"associated"| AD["AD"]
    BETA_AMYLOID["BETA_AMYLOID"] -->|"causes"| AD["AD"]
    PHOSPHORYLATED_TAU["PHOSPHORYLATED_TAU"] -->|"causes"| AD["AD"]
    SOD1["SOD1"] -->|"associated"| AD["AD"]
    style AD fill:#ef5350,stroke:#4fc3f7,stroke-width:2px,color:#e0e0e0

Outgoing (1238)

Target	Relation	Type	Str
neurodegeneration	causes	phenotype	0.87
memory_loss	causes	phenotype	0.72
TAU	associated_with	protein	0.72
IMMUNE_TOL	causes	phenotype	0.72
DEMENTIA	causes	disease	0.72
CHOLINERGIC_TRANSMISSION	associated_with	pathway	0.64
PROTEOME	regulates	pathway	0.64
cholinergic_transmission	inhibits	pathway	0.64
INFLAMMASOME	regulates	pathway	0.60
MAO	inhibits	gene	0.60
RAS	inhibits	gene	0.60
NLRP3	enhances	gene	0.60
NEUROINFLAMMATION	causes	pathway	0.60
CX3CR1	co_discussed	gene	0.60
STING	targets	gene	0.60
GRN	associated_with	gene	0.60
INFLAMMASOME	enhances	pathway	0.60
MAO	associated_with	gene	0.60
FUS	mediates	gene	0.60
FUS	targets	gene	0.60
NLRP3	activates	gene	0.60
AKT	enhances	gene	0.60
TFEB	co_discussed	gene	0.60
TFEB	activates	gene	0.60
MICROGLIA	mediates	cell_type	0.60
HD	co_discussed	gene	0.60
HUNTINGTON'S DISEASE	co_discussed	disease	0.60
HD	regulates	gene	0.60
APOE	disrupts	gene	0.60
ALZHEIMER'S DISEASE	expresses	disease	0.60
MICROGLIA	inhibits	cell_type	0.60
MAPT	co_discussed	gene	0.60
NLRP3	causes	gene	0.60
GFAP	activates	gene	0.60
ERK	activates	gene	0.60
FUS	co_discussed	gene	0.60
GSK3B	activates	gene	0.60
LRP1	activates	gene	0.60
MAPT	activates	gene	0.60
NFKB	activates	gene	0.60
FRONTOTEMPORAL DEMENTIA	co_discussed	disease	0.60
FTD	co_discussed	gene	0.60
CLU	regulates	gene	0.60
MBP	regulates	gene	0.60
BIN1	protects_against	gene	0.60
BIN1	inhibits	gene	0.60
LEWY BODY DEMENTIA	co_discussed	disease	0.60
LRRK2	associated_with	gene	0.60
PSEN2	associated_with	gene	0.60
DOPAMINERGIC	co_discussed	cell_type	0.60

Incoming (271)

Source	Relation	Type	Str
entities-ros	associated_with	wiki	0.00
entities-atp7b-gene	associated_with	wiki	0.00
entities-histone-methylation	associated_with	wiki	0.00
TDP-43	associated_with	protein	0.95
30541566	were increased in	paper	0.90
41660275	elevated in	paper	0.90
30541566	was highly increased in	paper	0.90
41660275	significantly elevated in	paper	0.90
41660275	positively correlated in CN but attenuated in	paper	0.90
TAU	associated_with	entity	0.90
30541566	was reduced in early stages and highly increased in	paper	0.90
30541566	were significantly higher in	paper	0.90
biomarkers-adpd-2026-blood-biomarkers	describes	wiki	0.90
APOE ε4	risk_factor_for	gene	0.90
APOE	associated_with	entity	0.85
MIR-146A	associated_with	mirna	0.80
SOD1	associated_with	gene	0.72
PHOSPHORYLATED_TAU	causes	protein	0.72
BETA_AMYLOID	causes	protein	0.72
resveratrol	targets	drug	0.70
entities-dian-observational-study	associated_with	wiki	0.65
entities-ltp	associated_with	wiki	0.65
entities-neprilysin	associated_with	wiki	0.65
T2D	associated_with	disease	0.64
NEUROINFLAMMATION	contributes_to	phenotype	0.64
AGE	associated_with	phenotype	0.64
MICROGLIA	associated_with	cell_type	0.64
TAU	causes	protein	0.64
SNCA	associated_with	gene	0.64
T2DM	associated_with	disease	0.64
HTL9936	treats	drug	0.64
PARK7	associated_with	gene	0.64
ACHE	mediates	gene	0.60
ACHE	causes	gene	0.60
ABCA1	activates	gene	0.60
ACHE	enhances	gene	0.60
AB	activates	gene	0.60
ABCA1	enhances	gene	0.60
ABCA1	causes	gene	0.60
ACHE	co_discussed	gene	0.60
ABCA1	associated_with	gene	0.60
AB	co_discussed	gene	0.60
ABCA1	interacts_with	gene	0.60
ABCA1	transports	gene	0.60
ABCA1	expresses	gene	0.60
ABCA1	regulates	gene	0.60
AB	targets	gene	0.60
ACHE	markers	gene	0.60
ABCA1	co_discussed	gene	0.60
ACHE	associated_with	gene	0.60

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
LPS-TLR4-NF-κB Signaling Cascade as Therapeutic Target	7.200	neurodegeneration	Gut-Brain Axis in Parkinson's Disease: M
Closed-loop optogenetic targeting PV interneurons to restore	0.944	Alzheimer's disease	Circuit-level neural dynamics in neurode
Plasma p-tau217-Triggered Exosome Dosing Maximizes lncRNA-00	0.938	molecular neurobiology	View
Closed-loop focused ultrasound targeting CA1 PV interneurons	0.927	Alzheimer's disease	Circuit-level neural dynamics in neurode
SASP-Mediated Complement Cascade Amplification	0.910	neurodegeneration	Senolytic therapy for age-related neurod

Closed-loop focused ultrasound targeting EC-II SST interneur	0.900	Alzheimer's disease	Circuit-level neural dynamics in neurode
Closed-loop tACS targeting EC-II SST interneurons to block t	0.896	Alzheimer's disease	Circuit-level neural dynamics in neurode
Complement Cascade Inhibition Synaptic Protection	0.867	neurodegeneration	View
Closed-loop tACS targeting EC-II PV interneurons to enhance	0.867	Alzheimer's disease	Circuit-level neural dynamics in neurode
Closed-loop focused ultrasound targeting EC-II PV interneuro	0.863	Alzheimer's disease	Circuit-level neural dynamics in neurode
Closed-loop tACS targeting EC-II PV interneurons to suppress	0.857	Alzheimer's disease	Circuit-level neural dynamics in neurode
Senescent Cell ASM-Complement Cascade Intervention	0.852	neurodegeneration	Lipid raft composition changes in synapt
Circadian Glymphatic Entrainment via Targeted Orexin Recepto	0.841	neurodegeneration	Perivascular spaces and glymphatic clear
Sequential Iron Chelation (Deferoxamine) and GPX4 Restoratio	0.838	neurodegeneration	View
Closed-loop tACS targeting EC-II parvalbumin interneurons to	0.831	Alzheimer's disease	Circuit-level neural dynamics in neurode
Real-time gamma-guided transcranial focused ultrasound targe	0.827	Alzheimer's disease	Circuit-level neural dynamics in neurode
P2RX7-Mediated Exosome Secretion Blockade	0.807	neurodegeneration	Tau propagation mechanisms and therapeut
IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microgl	0.806	neuroinflammation	How do oligodendrocytes initiate neuroin
Selective APOE4 Degradation via Proteolysis Targeting Chimer	0.795	neurodegeneration	APOE4 structural biology and therapeutic
Closed-loop tACS targeting entorhinal cortex layer II SST in	0.784	Alzheimer's disease	Circuit-level neural dynamics in neurode
ALOX15-Driven Enzymatic Ferroptosis in AD Oligodendrocytes v	0.777	Alzheimer's Disease	Cell type vulnerability in Alzheimers Di
TBK1-OPTN-NDP52 Phospho-Cascade Coordinates Multi-Organelle	0.772	neurodegeneration	How do different organelle-specific auto
Circadian Clock-Autophagy Synchronization	0.763	neurodegeneration	Sleep disruption as cause and consequenc
PARP1-NAD+-AIF bioenergetic collapse drives a self-amplifyin	0.760	neurodegeneration	What mechanisms drive the self-amplifyin
Senescence-Activated NAD+ Depletion Rescue	0.755	neurodegeneration	Senolytic therapy for age-related neurod
Dual-Circuit Tau Vulnerability Cascade	0.754	neuroscience	Circuit-level neural dynamics in neurode
Selective blockade of classical-pathway activation downstrea	0.750	neurodegeneration	Does C1q function differ based on subcel
Metabolic NAD+ Salvage Pathway Enhancement Through NAMPT Ove	0.745	neurodegeneration	Epigenetic reprogramming in aging neuron
Circadian-Synchronized Proteostasis Enhancement	0.744	neurodegeneration	Digital biomarkers and AI-driven early d
Complement-SASP Amplification Cascade as Mechanistic Link	0.741	neurodegeneration	Why have anti-Aβ clinical trials failed

Mentioning Analyses (30)

Scientific analyses that reference this entity

Blood-brain barrier permeability changes as early biomarkers for neurodegenerati

neurodegeneration | 2026-04-26 | 5 hypotheses Top: 0.712

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

neurodegeneration | 2026-04-25 | 6 hypotheses Top: 0.583

What are the optimal oxygen pressure, duration, and frequency parameters for HBO

neurodegeneration | 2026-04-25 | 7 hypotheses Top: 0.640

Does the cancer-cystatin-C-TREM2 pathway protect against tau pathology and other

neurodegeneration | 2026-04-25 | 8 hypotheses Top: 0.640

How does parthenolide specifically modulate ADORA2A signaling to produce antidep

neuropharmacology | 2026-04-25 | 3 hypotheses Top: 0.640

Experiments (10)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
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
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
Complement and microglia mediate early synapse loss in Alzheimer mouse models. [PMID:27033548]	Hong S, Beja-Glasser VF, Nfonoyim BM, Fr	Science	2016	1
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 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
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
Microglia activation orchestrates CXCL10-mediated CD8+ T cell recruitment to pro [PMID:40404995]	Groh J, Feng R, Yuan X, Liu L, Klein D,	Nature neuroscience	2025	0
Chrysophanol Attenuates Cognitive Impairment, Neuroinflammation, and Oxidative S [PMID:40728692]	Khan JZ, Zainab SR, Alattar A	Neurochem Res	2025	0
Qingda granule alleviates cerebral ischemia/reperfusion injury by inhibiting TLR [PMID:38184025]	Unknown	Journal of ethnopharmacology	2024	0
Botulinum Neurotoxin Induces Neurotoxic Microglia Mediated by Exogenous Inflamma [PMID:38342616]	Ambrin G, Kang YJ, Van Do K, Lee C, Sing	Advanced science (Weinheim, Ba	2024	0
Development of Injectable Thermosensitive Nanocomposite Hydrogel for Ratiometric [PMID:38456789]	["Zhu J", "Wei R", "Hu G", "Wang H", "Wa	Small (Weinheim an der Bergstr	2024	0
Sirt6 protects retinal ganglion cells and optic nerve from degeneration during a [PMID:38659223]	Xia F, Shi S, Palacios E, Liu W, Buscho	Molecular therapy : the journa	2024	0
The Role of Complement Dysregulation in Glaucoma. [PMID:38396986]	["Hoppe C", "Gregory-Ksander M"]	International journal of molec	2024	0

Debates (20)

Multi-agent debates referencing this entity

Blood-brain barrier permeability changes as early biomarkers for neurodegenerati

active · Rounds: 7 · Score: 0.00 · 2026-04-26

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

completed · Rounds: 5 · Score: 0.50 · 2026-04-25

What are the optimal oxygen pressure, duration, and frequency parameters for HBO

active · Rounds: 4 · Score: 0.68 · 2026-04-25

Does the cancer-cystatin-C-TREM2 pathway protect against tau pathology and other

active · Rounds: 4 · Score: 0.66 · 2026-04-25

How does parthenolide specifically modulate ADORA2A signaling to produce antidep

active · Rounds: 4 · Score: 0.66 · 2026-04-25

Does pericyte senescence drive BBB breakdown or result from neurodegeneration as

active · Rounds: 4 · Score: 0.68 · 2026-04-25

Which cell types show the greatest vulnerability in Alzheimer's disease accordin

closed · Rounds: 4 · Score: 0.75 · 2026-04-22

APOE4 is the strongest genetic risk factor for late-onset AD. How APOE4 specific

closed · Rounds: 4 · Score: 0.78 · 2026-04-22

The abstract identifies APOE4 association with increased TDP-43 pathology but th

closed · Rounds: 4 · Score: 0.61 · 2026-04-21

The debate raised this developmental hypothesis but couldn't resolve the mechani

closed · Rounds: 4 · Score: 0.71 · 2026-04-21

Related Research

Hypotheses and analyses mentioning AD in their description or question text

AD

Understanding Entity Pages

Summary

Wiki Pages (21)

Infectious Triggers in Alzheimer's Disease

Epigenetic Dysregulation Comparison -- AD/PD/ALS/FTD/HD

PMN310 Anti-Amyloid for AD (NCT06750432)

Epigenetic-Metabolic Coupling: SIRT1 Activator + NAD+ Precursor

Lipid Metabolism Dysfunction Comparison — AD/PD/ALS/FTD/HD

NAD+ Precursors for Neurodegeneration

Autophagy-Lysosomal Impairment Comparison — AD/PD/ALS/FTD/HD

Neuroinflammation Across AD, PD, ALS, FTD, and HD

AD Biomarker-to-Mechanism Mapping

AD Cure Roadmap — Integrated Timeline

Alzheimer's Drug Discovery Foundation (ADDF)

Infantile Neuroaxonal Dystrophy (INAD)

Autophagy Failure Comparison -- AD/PD/ALS/FTD/HD

KarXT+EC Phase 3 (NCT07011732): Enhanced Formulation for AD Agitation

AD Therapeutic Approaches Ranked Scorecard

Methylphenidate + iTBS for Apathy in AD (PRIME Trial)

CORT108297 Phase 2 (NCT04601038) - Stress Attenuation in AD

DBS Nucleus Basalis Trial (NCT07218081): Deep Brain Stimulation for AD

Tricaprilin Phase 3 ALTER-AD Study (NCT05809908)

TEAD1 — TEA Domain Transcription Factor 1

Section 103: Sirtuin Pathway and NAD+-Dependent Deacetylases in CBS/PSP

Pathway Diagram

Outgoing (1238)

Incoming (271)

Targeting Hypotheses (30)

Mentioning Analyses (30)

Blood-brain barrier permeability changes as early biomarkers for neurodegenerati

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

What are the optimal oxygen pressure, duration, and frequency parameters for HBO

Does the cancer-cystatin-C-TREM2 pathway protect against tau pathology and other

How does parthenolide specifically modulate ADORA2A signaling to produce antidep

Does pericyte senescence drive BBB breakdown or result from neurodegeneration as

Neuroinflammation Biomarker Panel for Early AD Detection

Microglial subtypes in neurodegeneration — friend vs foe

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

Analyze the spectrum of microglial activation states (DAM, homeostatic, inflamma

scRNA-seq Processing and Cell Type Annotation of AD Brain

Gene Regulatory Network Inference in Alzheimer's Disease

Statistical Fine-Mapping of AD GWAS Loci to Identify Causal Variants

Variant Annotation and Prioritization of AD Risk Loci

Polygenic Risk Score Analysis for Late-Onset Alzheimer's Disease

Survival Analysis of AD Patient Cohorts: Prognostic Markers and Time-to-Dementia

Clinical Trial Landscaping for Alzheimer's Disease Therapeutics

Proteomics Differential Expression in AD CSF and Brain Tissue

Multi-modal Biomarker Panel Design for Early AD Detection

Cell-Cell Communication Analysis in AD Brain Microenvironment

Gene Co-expression Network Analysis of AD Progression Modules

Spatial Transcriptomics Analysis of Alzheimer's Disease Brain Regions

Do β-amyloid plaques and neurofibrillary tangles cause or result from cholinergi

Why have numerous phase 3 clinical trials failed despite advances in understandi

Systemic immune profiling in neurodegeneration: peripheral inflammation as drive

Lipid metabolism dysregulation in Alzheimer's disease: membrane rafts, gangliosi

Metabolomic signatures of neurodegeneration: metabolic reprogramming in aging br

What are the cell-type-specific transcriptomic signatures of vulnerability in SE

What molecular mechanisms mediate HDAC9's effects on Aβ deposition and synaptic

What molecular mechanisms mediate HDAC9's effects on Aβ deposition and synaptic

Experiments (10)

Related Papers (20)

Debates (20)

Blood-brain barrier permeability changes as early biomarkers for neurodegenerati

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

What are the optimal oxygen pressure, duration, and frequency parameters for HBO

Does the cancer-cystatin-C-TREM2 pathway protect against tau pathology and other

How does parthenolide specifically modulate ADORA2A signaling to produce antidep

Does pericyte senescence drive BBB breakdown or result from neurodegeneration as

Which cell types show the greatest vulnerability in Alzheimer's disease accordin

APOE4 is the strongest genetic risk factor for late-onset AD. How APOE4 specific

The abstract identifies APOE4 association with increased TDP-43 pathology but th

The debate raised this developmental hypothesis but couldn't resolve the mechani

Related Research

Closed-loop focused ultrasound targeting EC-II SST interneurons to restore gamma

Closed-loop tACS targeting EC-II SST interneurons to block tau propagation and r

Complement Cascade Inhibition Synaptic Protection

Closed-loop tACS targeting EC-II PV interneurons to enhance perisomatic inhibiti

Closed-loop focused ultrasound targeting EC-II PV interneurons to restore theta-

Closed-loop tACS targeting EC-II PV interneurons to suppress burst firing and bl