mechanism 1,702 words KG: ent-gene-961a77ee 2026-04-01
kind:section:mechanismsevidence:strongmechanismsection:mechanismsstate:publishedmodel:alzheimermodel:amyloid
Contents

APP/PS1 Double Transgenic Mouse Model

🔬 Protein Info
Gene Symbolent-gene-961a77ee
Primary ExpressionHigh-level expression in neurons throughout the brain [@radde2006]
Locationtransmembrane domain II of PS1 ( residue M146)
EffectSubtle alteration of γ-secretase substrate specificity
OriginOne of the most common FAD PSEN1 mutations, first identified in families with early-onset AD
Aβ elevation3-5 fold increase in total Aβ production [@moechars1999]
ResultShifts Aβ production toward the more aggregation-prone Aβ42 species
InheritanceAutosomal dominant, early-onset familial AD [@borchelt1996]
Aβ shiftIncreases Aβ42/Aβ40 ratio (~2-3 fold)
Pathology onsetSimilar to PS1ΔE9, plaques detectable by 5-8 months
Co-integrationBoth transgenes integrated on separate chromosomes
PromoterMouse prion protein (PrP) promoter drives neuronal expression
BackgroundC57BL/6J x C3H hybrid background
OnsetPlaques detectable by 6 months of age
DistributionCortex and hippocampus first, spreading to striatum later
Plaque typesBoth diffuse and neuritic (cored) plaques
KG Connections4 knowledge graph edges
DatabasesGeneCardsUniProtNCBI GeneHPASTRING

Knowledge Graph

Related Hypotheses (28)

Multi-Target Hypothesis: Aβ-Induced Cholinergic Damage is Pa
Score: 0.70
Selective Cholinergic Protection via APP Pathway Modulation
Score: 0.43
Circadian Glymphatic Entrainment via Targeted Orexin Recepto
Score: 0.62
Digital Twin-Guided Metabolic Reprogramming
Score: 0.61
Multi-Modal Stress Response Harmonization
Score: 0.60

Related Analyses (30)

CRISPR-based therapeutic approaches for neurodegenerative di
neurodegeneration · completed
CRISPR-based therapeutic approaches for neurodegenerative di
neurodegeneration · archived
Selective vulnerability of entorhinal cortex layer II neuron
neurodegeneration · archived
4R-tau strain-specific spreading patterns in PSP vs CBD
neurodegeneration · archived
TDP-43 phase separation therapeutics for ALS-FTD
neurodegeneration · archived

Related Experiments (24)

Plasma ATN biomarkers across AD continuum in Chilean cohort
clinical · proposed · Score: 0.95
Creation and validation of 3xAD-ChAT-Cre mouse model
validation · proposed · Score: 0.90
Adoptive transfer of TCRAβ-Tregs in AD mouse model
validation · proposed · Score: 0.90
Chi3l1 deletion in APP/PS1 mouse model of Alzheimer's diseas
validation · proposed · Score: 0.95
Anti-ASC antibody intracerebroventricular injection in APP/P
validation · proposed · Score: 0.95

Knowledge Graph (4 edges)

ent-gene-961a77ee data_in ad_genetic_risk_loci:APP
ent-gene-961a77ee data_in benchmark_ot_ad_answer_key:APP
ad_genetic_risk_loci:APP data_in ent-gene-961a77ee
benchmark_ot_ad_answer_key:APP data_in ent-gene-961a77ee