Protein / target
Amyloid-beta precursor protein
Protein at a glance
Biological role
Serine-type endopeptidase inhibitor activity
Primary system
Nervous system
Strongest disease association
Alzheimer disease type 1
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
3 approved · 10 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Interaction between APP molecules on neighboring cells promotes synaptogenesis (PubMed:25122912). Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(o) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1 (By similarity). By acting as a kinesin I membrane receptor, plays a role in axonal anterograde transport of cargo towards synapses in axons (PubMed:17062754, PubMed:23011729). Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1
Subcellular location
Domains and Gene Ontology detail (128)Hide
Domains & features
Gene Ontology
- Camyloid-beta complex
- Castrocyte projection
- Caxon
- Ccell surface
- Cclathrin-coated pit
- Ccytoplasm
- Ccytosol
- Cdendrite
- Cdendritic shaft
- Cdendritic spine
- Cearly endosome
- Cearly endosome membrane
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Synaptic signalling
- ·Functions as a cell surface receptor and performs physiological functions on the surface…
- ·synapse
- ·modulation of excitatory postsynaptic potential
- ·positive regulation of synaptic transmission, cholinergic
Transcriptional regulation
- ·Functions as a cell surface receptor and performs physiological functions on the surface…
- ·negative regulation of gene expression
- ·positive regulation of gene expression
- ·positive regulation of transcription by RNA polymerase II
Cell adhesion
- ·Functions as a cell surface receptor and performs physiological functions on the surface…
- ·cell adhesion
- ·extracellular matrix organization
Haemostasis
- ·platelet alpha granule lumen
- ·Platelet degranulation
- ·Aggregated β-amyloid interacts with fibrinogen
Immune signalling
- ·astrocyte activation involved in immune response
- ·positive regulation of inflammatory response
- ·positive regulation of interleukin-1 beta production
- ·positive regulation of interleukin-6 production
Apoptosis & cell death
- ·hippocampal neuron apoptotic process
- ·regulation of neuron apoptotic process
View underlying pathways (20)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Amyloid-beta A4 protein inhibitor
Appears in clinical studies involving dementia, Cognitive impairment, Alzheimer disease, Alzheimer disease
Amyloid-beta A4 protein binding agent
Appears in clinical studies involving Alzheimer disease, dementia, Alzheimer disease, Alzheimer disease
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 2,010 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 13 total
dementia · Cognitive impairment · Alzheimer disease
Alzheimer disease · Alzheimer disease · glaucoma
Alzheimer disease · Cognitive impairment · dementia
Alzheimer disease · Alzheimer disease · Alzheimer disease
Alzheimer disease · Alzheimer disease
age-related macular degeneration · atrophic macular degeneration · Alzheimer disease
Alzheimer disease · dementia · Alzheimer disease
Alzheimer disease · Alzheimer disease · Alzheimer disease
Alzheimer disease · Alzheimer disease
Alzheimer disease · Alzheimer disease · Alzheimer disease
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (17)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Indication expanded
Indication expansion: LECANEMAB-IRMB (BLA761375)
- Manufacturing updateEisai snares government manufacturing grant as it brings Leqembi packaging to UK with $65M expansion
- Regulatory approval
Approval: LECANEMAB-IRMB (BLA761375)
- Regulatory approval
Approval: Leqembi (EMA)
- New publicationRecent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.
- New publicationLecanemab: Appropriate Use Recommendations.
- New publicationLecanemab in Early Alzheimer's Disease.
- New publicationTwo Randomized Phase 3 Studies of Aducanumab in Early Alzheimer's Disease.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.