gene

APP

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about APP: 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.

6264Connections

13Hypotheses

25Analyses

50Outgoing

50Incoming

3Experiments

20Debates

Summary

Amyloid Precursor Protein (APP) is a type I transmembrane protein critical for neuronal development, synapse formation, and iron homeostasis. APP is cleaved by two competing pathways: the non-amyloidogenic pathway (alpha-secretase ADAM10) producing neuroprotective sAPPalpha, and the amyloidogenic pathway (BACE1 and gamma-secretase) producing amyloid-beta peptides (Abeta40 and Abeta42). Accumulation of Abeta42 triggers the amyloid cascade hypothesis of Alzheimer's disease. Over 50 familial AD mutations in APP increase Abeta42 production or aggregation propensity. APP is located on chromosome 21, explaining early-onset AD in Down syndrome. Current therapies target APP processing (BACE1 inhibitors, gamma-secretase modulators) or Abeta clearance (anti-amyloid antibodies like lecanemab and donanemab).

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🧬 Gene Info

Gene Symbol	APP
Full Name	Amyloid Precursor Protein
Chromosome	21q21.3
Protein Type	Protein
Function	is a type I transmembrane glycoprotein that plays a central role in the pathogenesis of Alzheimer's disease (AD).
Primary Expression	Ubiquitous, highest in brain
Molecular Weight	~110 kDa
Exons	18
Pathways	Amyloid, Angiogenesis, Apoptosis, Autophagy, Blood-Brain Barrier
UniProt ID	P05067
NCBI Gene ID	351
Ensembl ID	ENSG00000142192
OMIM	104760
GeneCards	APP
Human Protein Atlas	APP
Associated Diseases	AD, aging, Als, Alzheimer
Known Drugs/Compounds	Abeta, aducanumab, Atractylodes macrocephala, berberine, BERBERINE, D-520
Interactions	A2M, ABCA1, ABCA7, ACETYLCHOLINE, ACHE, ACSL4
SciDEX Hypotheses	Selective Cholinergic Protection via APP Pathway M Amyloid Precursor Protein Processing Modulation vi
KG Connections	4396 knowledge graph edges
Databases	GeneCards HPA STRING

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

📄 Experimental Structure

1AAP — 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 (21)

Knowledge base pages for this entity

Canonical Page

Pathway Diagram

graph TD
    subgraph Pathology["Pathology"]
        APP["APP"] -->|"associated with"| Cancer["Cancer"]
        APP["APP"] -->|"associated with"| Neurodegeneration["Neurodegeneration"]
        APP["APP"] -->|"associated with"| PSEN1["PSEN1"]
        APP["APP"] -->|"associated with"| Alzheimer_3["Alzheimer"]
        APP["APP"] -->|"associated with"| Als_4["Als"]
        APOE["APOE"] -->|"associated with"| APP["APP"]
        APOPTOSIS["APOPTOSIS"] -->|"associated with"| APP["APP"]
        ALZHEIMER_S_DISEASE_5["ALZHEIMER'S DISEASE"] -->|"associated with"| APP["APP"]
    end
    subgraph Signaling["Signaling"]
        APP["APP"] -->|"activates"| Alzheimer["Alzheimer"]
        APP["APP"] -->|"activates"| Als_2["Als"]
        APP_PS1["APP/PS1"] -.->|"inhibits"| APP["APP"]
        APP_PS1_6["APP/PS1"] -->|"activates"| APP["APP"]
    end
    subgraph Therapeutic["Therapeutic"]
        APP["APP"] -->|"therapeutic target"| Alzheimer_1["Alzheimer"]
        APP["APP"] -->|"therapeutic target"| Als["Als"]
        ALZHEIMER_S_DISEASE["ALZHEIMER'S DISEASE"] -->|"therapeutic target"| APP["APP"]
    end
    style APP fill:#4a1a6b,stroke:#4fc3f7,stroke-width:3px,color:#e0e0e0,font-weight:bold
    style Cancer fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Neurodegeneration fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Alzheimer fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Alzheimer_1 fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Als fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Als_2 fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style PSEN1 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Alzheimer_3 fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style Als_4 fill:#ef5350,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style APOE fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style APP_PS1 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style APOPTOSIS fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style ALZHEIMER_S_DISEASE fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style ALZHEIMER_S_DISEASE_5 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0
    style APP_PS1_6 fill:#4a1a6b,stroke:#4fc3f7,stroke-width:1px,color:#e0e0e0

Outgoing (3300)

Target	Relation	Type	Str
ad_genetic_risk_loci:APP	data_in	dataset_row	0.00
benchmark_ot_ad_answer_key:APP	data_in	dataset_row	0.00
ASTROCYTES	associated_with	cell_type	1.00
Dementia	activates	disease	1.00
CORTEX	associated_with	brain_region	1.00
ds-83b31ef18d49	provides_data_for	dataset	1.00
Neuroinflammation	activates	disease	1.00
Alzheimer	protects_against	disease	1.00
Alzheimer	associated_with	disease	1.00
NEUROINFLAMMATION	associated_with	gene	1.00
NEUROINFLAMMATION	activates	gene	1.00
HIPPOCAMPUS	associated_with	brain_region	1.00
Als	regulates	disease	1.00
BDNF	associated_with	gene	1.00
TNF	associated_with	gene	1.00
Neurodegeneration	associated_with	disease	1.00
ds-f50762b67605	provides_data_for	dataset	1.00
DEMENTIA	associated_with	gene	1.00
Neurodegeneration	activates	disease	1.00
Alzheimer	therapeutic_target	disease	1.00
ds-6784494f1741	provides_data_for	dataset	1.00
Inflammation	activates	disease	1.00
Apoptosis	activates	pathway	1.00
amyloid beta	expresses	protein	1.00
Alzheimer	treats	disease	1.00
TAU	associated_with	gene	1.00
Alzheimer	regulates	disease	1.00
Alzheimer	inhibits	disease	1.00
Alzheimer	expressed_in	disease	1.00
PSEN1	associated_with	gene	1.00
Als	therapeutic_target	disease	1.00
Als	associated_with	disease	1.00
MICROGLIA	associated_with	gene	1.00
Alzheimer	activates	disease	1.00
Cancer	associated_with	disease	1.00
Autophagy	activates	pathway	1.00
Als	activates	disease	1.00
Inflammation	inhibits	disease	1.00
Apoptosis	inhibits	pathway	1.00
GFAP	associated_with	gene	0.98
AUTOPHAGY	associated_with	gene	0.98
Amyloid-Beta Production	involved_in	process	0.98
NEURON	associated_with	gene	0.98
HIPPOCAMPUS	expressed_in	brain_region	0.95
ad_genetic_risk_loci:APP	data_in	dataset_row	0.95
Amyloid-β	associated_with	compound	0.95
Amyloid-Beta Peptide	associated_with	compound	0.95
Amyloid-Beta	associated_with	protein	0.95
benchmark_ot_ad_answer_key:APP	data_in	dataset_row	0.95
Alzheimer's disease	associated_with	disease	0.95

Incoming (2964)

Source	Relation	Type	Str
entities-norepinephrine	associated_with	wiki	0.00
benchmark_ot_ad_answer_key:APP	data_in	dataset_row	0.00
ad_genetic_risk_loci:APP	data_in	dataset_row	0.00
benchmark_ot_ad_answer_key:APP	data_in	dataset_row	0.00
ad_genetic_risk_loci:APP	data_in	dataset_row	0.00
ds-6784494f1741	data_in	dataset	1.00
APOPTOSIS	associated_with	gene	1.00
APOE	associated_with	gene	1.00
NEURODEGENERATION	associated_with	gene	1.00
ALZHEIMER	therapeutic_target	gene	1.00
NEURODEGENERATION	activates	gene	1.00
GENES	activates	gene	1.00
ALZHEIMER'S DISEASE	targets	gene	1.00
ALZHEIMER'S DISEASE	associated_with	gene	1.00
AMYLOID	associated_with	gene	1.00
INFLAMMATION	activates	gene	1.00
ds-f50762b67605	data_in	dataset	1.00
ALZHEIMER	activates	gene	1.00
APOPTOSIS	activates	gene	1.00
ALZHEIMER	associated_with	gene	1.00
AMYLOID	inhibits	gene	1.00
ds-83b31ef18d49	data_in	dataset	1.00
AMYLOID	activates	gene	1.00
APP/PS1	inhibits	gene	1.00
APP/PS1	activates	gene	1.00
ALZHEIMER	inhibits	gene	1.00
ALZHEIMER'S DISEASE	treats	gene	1.00
ALZHEIMER	treats	gene	1.00
ALZHEIMER	protects_against	gene	1.00
GENES	expressed_in	gene	1.00
AMYLOID	therapeutic_target	gene	1.00
ALZHEIMER'S DISEASE	protects_against	gene	1.00
AMYLOID-BETA	associated_with	gene	1.00
AMYLOID	degrades	protein	0.95
Γ-SECRETASE	cleaves	enzyme	0.95
MEPRIN Β	cleaves	enzyme	0.90
HOPS	regulates	protein	0.90
ALZHEIMER'S DISEASE	regulates	gene	0.90
SEPT8	modulates	protein	0.90
hyp-SDA-2026-04-12-20260411-082446-2c1c9e2d-1	targets_gene	hypothesis	0.90
ADAMTS5	cleaves	enzyme	0.90
ADAMTS4	cleaves	enzyme	0.90
BACE	associated_with	enzyme	0.90
Presenilin Complex	associated_with	protein	0.90
Platelets	expressed_in	cell_type	0.90
BACE1	associated_with	protein	0.90
oleanonic acid	downregulates	drug	0.90
Gamma-Secretase Complex	targets	enzyme	0.90
h-0d576989	targets	hypothesis	0.90
NEURODEGENERATION	expressed_in	gene	0.90

Targeting Hypotheses (13)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Endosomal trafficking defects are the common upstream lesion	0.730	neurodegeneration	What determines the temporal sequence of
Selective Cholinergic Protection via APP Pathway Modulation	0.629	neurodegeneration	Clinical Trial Landscaping for Alzheimer
Locus coeruleus degeneration gates whether cholinergic dysfu	0.620	neurodegeneration	What determines the temporal sequence of
Glycosaminoglycan Template Disruption Approach	0.597	neurodegeneration	Protein aggregation cross-seeding across
Synthetic Biology Approach: Designer Mitochondrial Export Sy	0.505	neurodegeneration	Mitochondrial transfer between neurons a

CX3CR1 PET with Nano-bodies for Microglial Surveillance Stat	0.477	biomarkers	What biomarkers can reliably detect micr
Lysosomal Accumulation-Induced V-ATPase Inhibition (Osmotic	0.470	neurodegeneration	Why do structurally diverse sugars (treh
Cdk5/p25-PSD-95 Phosphorylation Disrupts Synaptic Scaffoldin	0.455	neurodegeneration	Quantitative proteomics of the aging syn
Synaptic Vesicle Protein Phosphorylation Reprograms Release	0.455	neurodegeneration	Quantitative proteomics of the aging syn
AD fine-mapping identifies causal variants in microglia-spec	0.380	alzheimers	Statistical Fine-Mapping of AD GWAS Loci
APP Processing Compartmentalization Therapeutics	0.000	-	Lipid raft composition changes in synapt
Amyloid Precursor Protein Processing Modulation via Bacteria	0.000	-	Gut-Brain Axis Therapeutics for Alzheime
Novel CRISPR-based Therapies for Huntington's Disease: A Mul	0.000	neurodegeneration	-

Mentioning Analyses (25)

Scientific analyses that reference this entity

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

neurodegeneration | 2026-04-25 | 6 hypotheses Top: 0.387

Clinical Trial Landscaping for Alzheimer's Disease Therapeutics

neurodegeneration | 2026-04-16 | 1 hypotheses Top: 0.629

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

lipidomics | 2026-04-16 | 13 hypotheses Top: 0.802

Quantitative proteomics of the aging synapse: protein turnover and aggregation i

proteomics | 2026-04-16 | 19 hypotheses Top: 0.591

What molecular mechanisms link elevated sphingomyelin synthase activity to incre

neurodegeneration | 2026-04-15 | 1 hypotheses Top: 0.734

Experiments (3)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Plasma ATN biomarkers across AD continuum in Chilean cohort	clinical	Alzheimer's disease	0.950	Chilean older adults (n=318) w	proposed	N/A
Adoptive transfer of TCRAβ-Tregs in AD mouse model	validation	Alzheimer's disease	0.900	transgenic mice expressing chi	proposed	N/A
E2F coordination of G2/M transcriptional program	exploratory		0.750	endocycling mammalian cells	proposed	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year
Enhancing the efficiency of bone tissue regeneration by using a 3D printed scaff [PMID:41435437]	Ku CY, Chen YH, Lin CM, Chu YH, Ho YJ, L	Biomedical materials (Bristol,	2026
Cataract Aggravates Alzheimer-Like Pathologies and Cognitive Deficits in an APP/ [PMID:40580389]	Geng Z, Yu ZY, Tan J, Wang XY, Zeng GH e	Neurosci Bull	2026
Integrating biocatalysis with continuous flow: current status, challenges, and f [PMID:40639553]	Bai J, Huang C, Liu Y, Zheng X, Liu J et	J Adv Res	2026
Engineering chimeric signaling proteins for microbial whole-cell biosensors: fro [PMID:40903364]	Özer Bergman G, Mecacci S, Martins Dos S	Trends Biotechnol	2026
MTAP Deletion in Oncogenesis: A Synthetic Lethality Scenario. [PMID:41512197]	Rodon J, Johnson ML, George B, Shah PA,	Cancer Res	2026
HOPS disruption impairs APP trafficking and processing, promoting exosomal secre [PMID:41525887]	Draper D, George AE, Veenendaal T, van D	Neurobiol Dis	2026
TREM2 expression level is critical for microglial state, metabolic capacity and [PMID:41580393]	Feiten AF, Dahm K, Schlepckow K, van Len	Nat Commun	2026
APP-C31 pathology as a target in neurodegenerative diseases. [PMID:41639863]	Yip KC, Ho WF, Liu Y, Dawe GS	J Biomed Sci	2026
Decoding Alzheimer's disease through down syndrome: insights from a genetically [PMID:41709686]	Russell JK, Schlachetzki Z, Rafii MS	Curr Opin Neurol	2026
Apps for people with vision impairment: an international review of practitioner [PMID:41734772]	Gothwal VK, Miller A, Boon MY, Subramani	Clin Exp Optom	2026
Impaired TGFβ Signaling in Plaque-Associated Microglia. [PMID:41750318]	Krzyzan O, Kuhla A, Spittau B, Vidovic N	Biomolecules	2026
Design and synthesis of BAP-1 inhibitors. [PMID:41761813]	Zhang Z, Yang X	Pak J Pharm Sci	2026
Optimized bacterial expression of a synthetic BRIL antibody. [PMID:41842660]	Cooper BF, Isom GL	Acta Crystallogr F Struct Biol	2026
APP as an innate injury-response molecule. [PMID:41864298]	Olmsted ZT, Sofroniew MV	Neurobiol Dis	2026
CRISPR-Cas9 and next-generation gene editing strategies for therapeutic interven [PMID:41931258]	Khan MS, Zafar I, Jamal A, Bahwerth FS,	Acta Neurol Belg	2026
Akkermansia muciniphila reduces neuroinflammation and Aβ deposition via tryptoph [PMID:41715194]	Wang B, Pan M, Yang L, Xu J, Ye C, Li Y,	Alzheimer's research & therapy	2026
Alzheimer's disease basics: we all should know. [PMID:40639927]	Das S	Neurological research	2026
Cerebral FURIN deficiency impairs astrocytic lipophagy through ITGAV maturation. [PMID:41376284]	Xie XY, Wang L, Xie SQ, Zhou GF, Wen QX,	Autophagy	2026
Bacterial DNA methylases as novel molecular and synthetic biology tools: recent [PMID:40047928]	Flores-Fernández CN, O'Callaghan CA	Applied microbiology and biote	2025
Trichomonas vaginalis adhesion protein 65 facilitates human papillomavirus entry [PMID:41199321]	Mei X, Sheng W, Zhang Y, Tian W, Tian X,	Infectious diseases of poverty	2025

Debates (20)

Multi-agent debates referencing this entity

Second debate: Microglial TREM2-SYK Pathway Enhancement

closed · Rounds: 4 · Score: 0.57 · 2026-04-28

Structured research brief (iter2): ω-3 Docosahexaenoic Acid (DHA) Epoxide Genera

archived · Rounds: 2 · Score: 0.64 · 2026-04-28

Extended debate: CYP46A1 Overexpression Gene Therapy

closed · Rounds: 6 · Score: 0.95 · 2026-04-27

Extended debate: Closed-loop transcranial focused ultrasound with 40Hz gamma ent

closed · Rounds: 6 · Score: 0.95 · 2026-04-27

Extended debate: Closed-loop tACS targeting EC-II SST interneurons to block tau

closed · Rounds: 6 · Score: 0.95 · 2026-04-27

Debate: Closed-loop transcranial focused ultrasound targeting entorhinal PV inte

closed · Rounds: 4 · Score: 0.65 · 2026-04-27

Debate: Chromatin Remodeling-Mediated Nutrient Sensing Restoration

closed · Rounds: 4 · Score: 0.46 · 2026-04-27

Debate: Closed-loop tACS targeting EC-II SST interneurons to block tau propagati

closed · Rounds: 4 · Score: 0.71 · 2026-04-27

Debate: Closed-loop transcranial focused ultrasound to restore hippocampal gamma

closed · Rounds: 4 · Score: 0.87 · 2026-04-27

Debate: Closed-loop tACS targeting EC-II PV interneurons to suppress burst firin

closed · Rounds: 4 · Score: 0.48 · 2026-04-27

Related Research

Hypotheses and analyses mentioning APP in their description or question text

APP

Understanding Entity Pages

Summary

Wiki Pages (21)

APP Protein

APP Flemish Mutation (APP Flemish)

Amyloid Precursor Protein (APP)

APP→Amyloid-beta→Plaque→Alzheimer's Disease Causal Chain

APP — Amyloid Precursor Protein

APP-BACE1-Fe65 Complex

Soluble Amyloid Precursor Protein Beta (sAPPβ)

APP Dutch Mutation (APP Dutch)

APP Swedish Mutation (APPswe)

APP/PS1 Double Transgenic Mouse Model

SORL1→APP Trafficking→Retromer Dysfunction→Aβ Accumulation→AD Causal Chain

Antiepileptic Drugs Modulate APP Trafficking

APP Processing and Amyloid-Beta Production

APP Gene Dosage Reduction Therapy for Down Syndrome

APP Mutations in Alzheimer's Disease

APP Gene

APP Arctic Mutation (APP Arctic)

APP Amyloid Pathway in Alzheimer's Disease

APP-Overexpressing Neurons

APP/PS1 Dual Transgenic Mouse Model

APPBP2 Gene

Pathway Diagram

Outgoing (3300)

Incoming (2964)

Targeting Hypotheses (13)

Mentioning Analyses (25)

Epigenetic clocks as biomarkers for Alzheimer disease and neurodegeneration

Clinical Trial Landscaping for Alzheimer's Disease Therapeutics

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

Quantitative proteomics of the aging synapse: protein turnover and aggregation i

What molecular mechanisms link elevated sphingomyelin synthase activity to incre

Why do p300/CBP inhibitors reduce both AD incidence and clinically diagnosed TBI

Epigenetic reprogramming in aging neurons

Tau propagation mechanisms and therapeutic interception points

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

Gene expression changes in aging mouse brain predicting neurodegenerative vulner

CRISPR-based therapeutic approaches for neurodegenerative diseases

Circuit-level neural dynamics in neurodegeneration

Cell type vulnerability in Alzheimers Disease (SEA-AD transcriptomic data)

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

CRISPR-based therapeutic approaches for neurodegenerative diseases

Epigenetic clocks and biological aging in neurodegeneration

Mitochondrial transfer between astrocytes and neurons

Senolytic therapy for age-related neurodegeneration

Autophagy-lysosome pathway convergence across neurodegenerative diseases

APOE4 structural biology and therapeutic targeting strategies

4R-tau strain-specific spreading patterns in PSP vs CBD

Blood-brain barrier transport mechanisms for antibody therapeutics

Mitochondrial transfer between neurons and glia

Lipid raft composition changes in synaptic neurodegeneration

What are the mechanisms by which gut microbiome dysbiosis influences Parkinson's

Experiments (3)

Related Papers (20)

Debates (20)

Second debate: Microglial TREM2-SYK Pathway Enhancement

Structured research brief (iter2): ω-3 Docosahexaenoic Acid (DHA) Epoxide Genera

Extended debate: CYP46A1 Overexpression Gene Therapy

Extended debate: Closed-loop transcranial focused ultrasound with 40Hz gamma ent

Extended debate: Closed-loop tACS targeting EC-II SST interneurons to block tau

Debate: Closed-loop transcranial focused ultrasound targeting entorhinal PV inte

Debate: Chromatin Remodeling-Mediated Nutrient Sensing Restoration

Debate: Closed-loop tACS targeting EC-II SST interneurons to block tau propagati

Debate: Closed-loop transcranial focused ultrasound to restore hippocampal gamma

Debate: Closed-loop tACS targeting EC-II PV interneurons to suppress burst firin

Related Research

CX3CR1 PET with Nano-bodies for Microglial Surveillance State Mapping

Lysosomal Accumulation-Induced V-ATPase Inhibition (Osmotic Trapping)

Cdk5/p25-PSD-95 Phosphorylation Disrupts Synaptic Scaffolding and Shifts APP Pro

Synaptic Vesicle Protein Phosphorylation Reprograms Release Probability and Inte

AD fine-mapping identifies causal variants in microglia-specific enhancers with

APP Processing Compartmentalization Therapeutics

Amyloid Precursor Protein Processing Modulation via Bacterial Enzyme Delivery