protein

AMYLOID-BETA

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about AMYLOID-BETA: 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.

1847Connections

30Hypotheses

2Analyses

50Outgoing

50Incoming

12Experiments

2Debates

Summary

Amyloid-beta (Abeta) peptides are 36-43 amino acid proteolytic fragments of the amyloid precursor protein (APP), generated by sequential cleavage by beta-secretase (BACE1) and gamma-secretase. The 42-residue form (Abeta42) is highly aggregation-prone and forms oligomers, protofibrils, and amyloid plaques that are pathological hallmarks of Alzheimer disease. Abeta aggregation triggers synaptic dysfunction, neuroinflammation via microglial activation, and oxidative stress. Clearance mechanisms include enzymatic degradation (neprilysin, IDE), microglial phagocytosis via TREM2, and blood-brain barrier transport via LRP1. Impaired clearance is a major contributor to sporadic AD. Therapeutic strategies include anti-Abeta antibodies (lecanemab, donanemab), BACE1 inhibitors, and gamma-secretase modulators.

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🔬 Protein Info

Gene Symbol	AMYLOID
GeneCards	AMYLOID
Human Protein Atlas	AMYLOID
Associated Diseases	Aging, Als, Alzheimer, Alzheimer Disease, ALZHEIMER'S DISEASE
Known Drugs/Compounds	DONANEMAB, LECANEMAB, MELATONIN, NICOTINAMIDE, RAPAMYCIN, SEMAGLUTIDE
Interactions	A2M, ABCA1, ABCA7, ABI3, ACE, ACETYLCHOLINE
KG Connections	4765 knowledge graph edges
Databases	GeneCards UniProt NCBI Gene HPA STRING

🧬 3D Structure Comparison — AMYLOID-BETA Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

1IYT — X-ray / Cryo-EM

🔮 AI Predicted Structure

P05067 — AlphaFold

Left: Experimental structure from RCSB PDB | Right: AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (1)

Knowledge base pages for this entity

Canonical Page

Amyloid-Beta (Aβ)

protein · 3168 words

→

Pathway Diagram

flowchart TD
    AMYLOID_BETA(["AMYLOID-BETA"])
    ALZHEIMER_S_DISEASE(["ALZHEIMER'S DISEASE"])
    Alzheimer["Alzheimer"]
    Als["Als"]
    Inflammation["Inflammation"]
    ALZHEIMER(["ALZHEIMER"])
    AMYLOID(["AMYLOID"])
    APP(["APP"])

    AMYLOID_BETA -->|"associated with"| ALZHEIMER_S_DISEASE
    AMYLOID_BETA -->|"associated with"| Alzheimer
    AMYLOID_BETA -->|"therapeutic target"| Alzheimer
    AMYLOID_BETA -->|"associated with"| Als
    AMYLOID_BETA -->|"activates"| Alzheimer
    AMYLOID_BETA -->|"therapeutic target"| Als
    AMYLOID_BETA -->|"activates"| Inflammation
    AMYLOID_BETA -->|"therapeutic target"| ALZHEIMER_S_DISEASE
    ALZHEIMER -->|"associated with"| AMYLOID_BETA
    AMYLOID -->|"activates"| AMYLOID_BETA
    AMYLOID -->|"associated with"| AMYLOID_BETA
    ALZHEIMER -->|"activates"| AMYLOID_BETA
    ALZHEIMER -->|"therapeutic target"| AMYLOID_BETA
    AMYLOID_BETA -->|"associated with"| APP
    AMYLOID -.->|"inhibits"| AMYLOID_BETA

    style AMYLOID_BETA fill:#006494,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0

Outgoing (1069)

Target	Relation	Type	Str
AMYLOID-BETA	encodes	protein	0.00
Als	therapeutic_target	disease	1.00
Alzheimer	therapeutic_target	disease	1.00
Alzheimer	associated_with	disease	1.00
ALZHEIMER'S DISEASE	therapeutic_target	gene	1.00
Alzheimer	activates	disease	1.00
Als	associated_with	disease	1.00
ALZHEIMER'S DISEASE	associated_with	gene	1.00
Inflammation	activates	disease	1.00
APP	associated_with	gene	1.00
Tau Aggregation	associated_with	process	0.95
Neuroinflammation	activates	disease	0.95
Alzheimer's Disease	associated_with	disease	0.95
Alzheimer's Disease	causes	disease	0.95
Alzheimer'S Disease	associated_with	disease	0.95
Apoptosis	associated_with	process	0.95
Neurodegeneration	activates	disease	0.95
Alzheimer's Disease	associated_with	disease	0.95
Astrocytes	associated_with	cell_type	0.95
Pro-Inflammatory Cytokine Release	causes	process	0.95
Early Alzheimer'S Disease	involved_in	disease	0.95
Alzheimer Disease	biomarker_for	disease	0.95
Alzheimer Disease	associated_with	disease	0.95
Alzheimer's Disease	causes	disease	0.95
Alzheimer's Disease	drives	disease	0.95
Alzheimer	regulates	disease	0.95
Alzheimer's Disease	biomarker_for	disease	0.95
Alzheimer Disease	biomarker_for	disease	0.90
Neuronal Death	causes	process	0.90
neuronal survival	suppresses	phenotype	0.90
Amyloidosis	drives	process	0.90
Plaque Accumulation	involved_in	process	0.90
Alzheimer's Disease	causes	disease	0.90
neuronal loss	drives	phenotype	0.90
Cognitive decline	causes	phenotype	0.90
apoptosis	causes	phenotype	0.90
Calcium Dysregulation	causes	process	0.90
Alzheimer's Disease	drives	disease	0.90
Hyperconnectivity	associated_with	phenotype	0.90
KIF5	binds	protein	0.90
Tau Spreading	associated_with	process	0.90
CEREBRAL HYPOMETABOLISM	causes	pathway	0.90
Alzheimer's Disease	contributes_to	disease	0.90
Alzheimer's Disease	biomarker_for	disease	0.90
microglia	activates	cell_type	0.90
ASTROCYTES	associated_with	cell_type	0.90
Protein Aggregation	involved_in	process	0.90
ALZHEIMER'S DISEASE	activates	gene	0.90
Alzheimer'S Disease Pathology	associated_with	process	0.88
Neuronal Function	inhibits	process	0.88

Incoming (778)

Source	Relation	Type	Str
entities-norepinephrine	interacts_with	wiki	0.00
entities-overview	interacts_with	wiki	0.00
entities-crenezumab	interacts_with	wiki	0.00
entities-histone-deacetylase	interacts_with	wiki	0.00
entities-glymphatic-system	interacts_with	wiki	0.00
entities-ferroptosis	interacts_with	wiki	0.00
entities-hsp90-protein	interacts_with	wiki	0.00
entities-microglia-in-neurodegeneration	interacts_with	wiki	0.00
entities-interleukin-6	interacts_with	wiki	0.00
entities-simufilam	interacts_with	wiki	0.00
entities-irs1	interacts_with	wiki	0.00
entities-complement-system	interacts_with	wiki	0.00
entities-gaba	interacts_with	wiki	0.00
AMYLOID-BETA	encodes	gene	0.00
ALZHEIMER	activates	gene	1.00
AMYLOID	activates	gene	1.00
ALZHEIMER	therapeutic_target	gene	1.00
AMYLOID	associated_with	gene	1.00
ALZHEIMER	associated_with	gene	1.00
TAU	associated_with	gene	1.00
AMYLOID	inhibits	gene	1.00
BISPECIFIC ANTIBODIES	associated_with	entity	0.95
Alzheimer's Disease	associated_with	disease	0.95
APP	associated_with	protein	0.95
LRP1	regulates	protein	0.95
Donanemab	targets	drug	0.95
Hearing Loss	causes	phenotype	0.92
MTOR	promotes	gene	0.90
APOE	upregulates	gene	0.90
Protein Aggregation	involved_in	process	0.90
Monoclonal Antibodies	targets	drug	0.90
Aducanumab	targets	drug	0.90
anti-amyloid therapy	prevents	drug	0.90
HSPG2	co-localizes_with	gene	0.90
Lecanemab	targets	drug	0.90
ceramide	contributes_to	compound	0.90
TAU	interacts_with	protein	0.90
Bispecific Antibodies	targets	drug	0.90
Hearing Loss	upregulates	phenotype	0.90
APOE	associated_with	gene	0.90
PSEN1	produces	protein	0.90
Donanemab	targets	drug	0.90
LRP1-Targeted Polymersomes	treats	drug	0.90
ASTROCYTES	associated_with	cell_type	0.90
Donanemab	targets	drug	0.90
Lecanemab	targets	drug	0.90
glymphatic pathway	involved_in	pathway	0.90
autophagy	degrades	process	0.90
Glymphatic System	involved_in	process	0.90
Gangliosides	interacts_with	compound	0.90

Targeting Hypotheses (30)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Closed-loop optogenetic targeting PV interneurons to restore	0.952	Alzheimer's disease	Circuit-level neural dynamics in neurode
TREM2-Deficient Microglia as Drivers of Amyloid Plaque Toxic	0.827	neurodegeneration	Legacy Pre-Pipeline Hypothesis Import
Closed-loop transcranial focused ultrasound to restore hippo	0.827	Alzheimer's disease	Circuit-level neural dynamics in neurode
CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-S	0.811	neurodegeneration	What are the cell-type-specific transcri
Exposed amyloidogenic segments (β-sheet propensity residues)	0.790	protein biochemistry	Do chaperones selectively recognize path

Vicious Cycle Hypothesis: Cholinergic Dysfunction Exacerbate	0.785	-	Do β-amyloid plaques and neurofibrillary
PINK1/Parkin–TREM2 Axis: Convergent Mitophagy Failure Unifie	0.780	neurodegeneration	-
Direct Toxicity Hypothesis: β-Amyloid Directly Impairs Choli	0.769	-	Do β-amyloid plaques and neurofibrillary
Test: TREM2 enhances amyloid clearance	0.755	-	Test Hypothesis Fixtures
Stage-Specific TREM2 Biomarker-Guided Switching — Agonist in	0.735	Alzheimer's disease	TREM2 agonism vs antagonism in DAM micro
Bacterial Curli Amyloid → Nucleation of α-Synuclein Misfoldi	0.720	neurodegeneration	What are the mechanisms by which gut mic
Test: TREM2 enhances amyloid clearance	0.712	-	Test Hypothesis Fixtures
Excess orexin-A worsens AD cognition through wake-driven amy	0.711	neurodegeneration	Orexin-A manipulation in AD cognition an
Microglial TREM2 Activation Reduces Amyloid-Associated Neuro	0.710	neurodegeneration	Test Preregistration Analysis
Test: TREM2 enhances amyloid clearance	0.705	-	Test Hypothesis Fixtures
NRF2-Mediated Proteostatic Convergence: Shared Oxidative Str	0.700	neurodegeneration	-
APOE ε4 Drives Lipid Droplet Accumulation in a Unique Lipid-	0.685	Alzheimer disease	APOE ε4 Lipid Metabolism Differences in
TREM2 Microglial Activation Rescues Amyloid Clearance in AD	0.682	neurodegeneration	Test Hypothesis Fixtures
Arginine Methylation Loss on FUS RGG Domains Drives Irrevers	0.676	ALS	Biophysical Determinants Shifting FUS/TD
Test: TREM2 enhances amyloid clearance	0.655	-	Test Hypothesis Fixtures
Amyloid-beta induces secondary pericyte senescence after con	0.640	neurodegeneration	Does pericyte senescence drive BBB break
Stage-Selective TREM2 Agonism — Boosting DAM Phagocytosis in	0.637	Alzheimer's disease	TREM2 agonism vs antagonism in DAM micro
Test: TREM2 enhances amyloid clearance	0.637	-	Test Hypothesis Fixtures
Pericyte senescence is sufficient to weaken the BBB even wit	0.630	neurodegeneration	Does pericyte senescence drive BBB break
APOE4-microglial complement signaling causes cholinergic-enr	0.630	neurodegeneration	What determines the temporal sequence of
H1: TREM2 Agonism to Redirect APOE4-Enhanced Microglia from	0.626	neurodegeneration	TREM2 in Alzheimer's Disease: Mechanisms
sex-divergent microglial activation states and X-linked immu	0.626	neurodegeneration	Sex-Specific Microglial States in Amyloi
RNA-binding protein condensate maturation from reversible ph	0.626	neurodegeneration	Causal Sequence of TDP-43 Nuclear Cleara
RNA-binding protein condensate maturation from reversible ph	0.626	neurodegeneration	Biophysical Determinants Shifting FUS/TD
Microglial ACE Enhancement for Amyloid Clearance	0.622	neurodegeneration	Gene expression changes in aging mouse b

Mentioning Analyses (2)

Scientific analyses that reference this entity

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

neurodegeneration | 2026-04-12 | 1 hypotheses Top: 0.566

Metabolomic signatures of neurodegeneration and energy metabolism dysfunction

neurodegeneration | 2026-04-04 | 0 hypotheses

Experiments (12)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Feasibility	Model	Status	Est. Cost
TREM2 KO amyloid pathology study	validation	Alzheimers Disease	0.800	0.00	Mouse (5xFAD/TREM2-/-)	completed	N/A
Closed-loop tFUS Enhances Glymphatic Clearance and Restores CA1 PV Int	in_vivo	Alzheimer's disease	0.765	0.55	APP/PS1 mice 8-11 months (n=10	abandoned	$125,000
Single nuclei transcriptomic and epigenomic profiling of 84 donors acr	gene_expression	Alzheimer's disease	0.500	0.00	human	extracted	N/A
The Seattle Alzheimer's Disease Brain Cell Atlas (SEA-AD) integrates n	neuropathology	Alzheimer's disease	0.500	0.00	human	extracted	N/A
In late life, NfL demonstrated the strongest association with incident	clinical	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Complex gene expression differences were identified, ranging from glob	gene_expression	Alzheimer's disease	0.500	0.00	post_mortem_brain	extracted	N/A
A subset of donors with particularly severe cellular and molecular phe	clinical	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Midlife hypertension was associated with 0.15-SD faster NfL increase a	clinical	Alzheimer's disease	0.500	0.00	human	extracted	N/A
A subset of donors exhibited particularly severe cellular and molecula	computational	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Cell type-specific analysis identified early-phase loss of somatostati	gene_expression	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Single-cell/multiomics analysis of 84 human post-mortem brains reveale	computational	Alzheimer's disease	0.500	0.00	human	extracted	N/A
Temporal analysis of gene expression differences across disease progre	gene_expression	Alzheimer's disease	0.500	0.00	human	extracted	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Integrative Multiomics Insights into the Genetic and Epigenetic Architecture of [PMID:41422555]	Mishra AK, Jain S	ACS Chem Neurosci	2026
The association of Alzheimer's disease-related SNPs with mild cognitive impairme [PMID:41606232]	Xie Z, Tu W, Ye XF, Hua L, Zhang X et al	Sci Rep	2026
Genetic risk factors of late-onset Alzheimer's disease: Insights into pathophysi [PMID:41622452]	Akkaoui J, Devadoss D, Rodriguez MD, Ari	Neural Regen Res	2026
Genetic Burden and <i>APOE</i> Methylation in a Korean Multi-Generational Alzhei [PMID:41745359]	Eom Je-Hyun; Cho Mu-Yeol; Kim Ji-Won; Ki	Journal of personalized medici	2026
Genetic Architecture of Cognitive Resilience in Alzheimer's Disease: Mechanisms, [PMID:41893052]	Burdman Gabriel; Akkaoui Juliet; Colon N	Neurology international	2026
Posttraumatic stress disorder is associated with Alzheimer's disease-relevant mo [PMID:41960318]	Seijo MA, Yohannes PA, Rogers AL, Gonzal	Res Sq	2026
Genetic risk factors of late-onset Alzheimer's disease: Insights into pathophysi [PMID:41622452]	Akkaoui J, Devadoss D, Rodriguez MD, Ari	Neural regeneration research	2026
Genetic Architecture of Cognitive Resilience in Alzheimer's Disease: Mechanisms, [PMID:41893052]	["Burdman G", "Akkaoui J", "Colon N", "P	Neurology international	2026
Retinal Müller glia alterations and their impact on ocular glymphatic clearance [PMID:41603340]	Das G, Raghunathan R, Wang L	J Alzheimers Dis	2026
The Glymphatic-Venous Axis in Brain Clearance Failure: Aquaporin-4 Dysfunction, [PMID:41226584]	["Costea D", "Dobrin N", "Tataru C", "To	International journal of molec	2025
Longitudinal changes of blood-brain barrier and transcytolemmal water exchange p [PMID:40089221]	Xiong C, Yu Z, Yin Y	Neuroimage	2025
The future of biomarkers for vascular contributions to cognitive impairment and [PMID:40542975]	Lennon MJ, Karvelas N, Ganesh A	Geroscience	2025
P-tau217 correlates with neurodegeneration in Alzheimer's disease, and targeting [PMID:38513667]	Zhang D, Zhang W, Ming C, Gao X, Yuan H,	Neuron	2024
The necroptosis cell death pathway drives neurodegeneration in Alzheimer's disea [PMID:38852117]	Balusu S, De Strooper B	Acta neuropathologica	2024
α7nAChR activation in AT2 cells promotes alveolar regeneration through WNT7B sig [PMID:37410546]	Unknown	JCI Insight	2023
Insulin Resistance and Diabetes Mellitus in Alzheimer's Disease. [PMID:34069890]	Burillo J, Marqués P, Jiménez B, Gonzále	Cells	2021
Improvement of glymphatic-lymphatic drainage of beta-amyloid by focused ultrasou [PMID:32999351]	Lee Y, Choi Y, Park EJ	Sci Rep	2020
Cholinergic Signaling via Muscarinic Receptors Directly and Indirectly Suppresse [PMID:30185628]	Unknown	Cancer discovery	2019
CHRNA7 Deletions are Enriched in Risperidone-Treated Children and Adolescents. [PMID:28817303]	Gillentine Madelyn A; White Janson J; Gr	Journal of child and adolescen	2017
Analysis of CHRNA7 rare variants in autism spectrum disorder susceptibility. [PMID:25655306]	Unknown	Am J Med Genet A	2015

Debates (2)

Multi-agent debates referencing this entity

How do metabolomic alterations in glucose metabolism, mitochondrial function, an

closed · Rounds: 4 · Score: 0.30 · 2026-04-21

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

closed · Rounds: 5 · Score: 0.67 · 2026-04-12

Related Research

Hypotheses and analyses mentioning AMYLOID-BETA in their description or question text

AMYLOID-BETA

Understanding Entity Pages

Summary

Wiki Pages (1)

Amyloid-Beta (Aβ)

Pathway Diagram

Outgoing (1069)

Incoming (778)

Targeting Hypotheses (30)

Mentioning Analyses (2)

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

Metabolomic signatures of neurodegeneration and energy metabolism dysfunction

Experiments (12)

Related Papers (20)

Debates (2)

How do metabolomic alterations in glucose metabolism, mitochondrial function, an

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

Related Research

Vicious Cycle Hypothesis: Cholinergic Dysfunction Exacerbates Amyloid Pathology

Direct Toxicity Hypothesis: β-Amyloid Directly Impairs Cholinergic Signaling

Test: TREM2 enhances amyloid clearance

Stage-Specific TREM2 Biomarker-Guided Switching — Agonist in Amyloid Phase, Anta

Bacterial Curli Amyloid → Nucleation of α-Synuclein Misfolding in Enteric Neuron

Test: TREM2 enhances amyloid clearance

Excess orexin-A worsens AD cognition through wake-driven amyloid production

Microglial TREM2 Activation Reduces Amyloid-Associated Neurotoxicity

Test: TREM2 enhances amyloid clearance

APOE ε4 Drives Lipid Droplet Accumulation in a Unique Lipid-Associated Microglia

TREM2 Microglial Activation Rescues Amyloid Clearance in AD

Arginine Methylation Loss on FUS RGG Domains Drives Irreversible Phase Transitio

Test: TREM2 enhances amyloid clearance