gene

LRP1

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about LRP1: 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.

1655Connections

12Hypotheses

9Analyses

50Outgoing

50Incoming

10Experiments

14Debates

Summary

Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor involved in endocytosis, cell signaling, and Aβ clearance across the blood-brain barrier. Implicated in Alzheimer disease pathogenesis through regulation of amyloid-beta transport and tau uptake.

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🧬 Gene Info

Gene Symbol	LRP1
Aliases	Low-density lipoprotein receptor-related protein 1, CD91
Protein Type	Receptor
Target Class	Receptor
Function	In the healthy nervous system, LRP1 functions as
Mechanism of Action	Modulation of receptor-mediated endocytosis and clearance pathways
Druggability	Low (0.39)
Clinical Stage	Phase III
Molecular Weight	600 kDa
Amino Acids	525 aa
Pathways	Aβ clearance, APOE trafficking, Endocytosis, MAPK, PI3K
UniProt ID	Q07954
GeneCards	LRP1
Human Protein Atlas	LRP1
Associated Diseases	Aging, Als, Alzheimer, Alzheimer's disease
Known Drugs/Compounds	MELATONIN
Interactions	ABCA1, abca2, ABCA2, ABCB1, ABI3, ACAT1
SciDEX Target	View Target Profile (6 clinical trials)
SciDEX Hypotheses	LRP1-Dependent Tau Uptake Disruption Astrocyte LRP1-mediated tau uptake and APOE4-depen LRP1-Dependent Tau Uptake Disruption (+4 more)
KG Connections	1655 knowledge graph edges
Databases	GeneCards NCBI Gene HPA STRING

🧬 3D Structure Comparison — LRP1 Experimental (PDB) vs Predicted (AlphaFold) — click to expand

📄 Experimental Structure

2FCW — X-ray / Cryo-EM

🔮 AI Predicted Structure

Q07954 — AlphaFold

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

Wiki Pages (20)

Knowledge base pages for this entity

Canonical Page

APOE contributes to Alzheimer's disease by regulating both beta-amyloid deposition

hypothesis · 2704 words

→

Pathway Diagram

graph TD
    LRP1["LRP1 Receptor"] -->|"Binds"| Ligands["APOE, Abeta, tPA"]
    LRP1 -->|"Mediates"| Endocytosis["Receptor-Mediated Endocytosis"]
    Endocytosis -->|"Internalizes"| Abeta["Abeta Peptides"]
    Abeta -->|"Degraded in"| Lysosome["Lysosomes"]
    LRP1 -->|"Expressed on"| BBB["Brain Endothelium"]
    BBB -->|"Efflux of"| Clearance["Abeta Clearance to Blood"]
    LRP1 -.Downregulation.-> Accumulation["Abeta Accumulation"]
    Accumulation -.Contributes to.-> AD["Alzheimer's Disease"]

Outgoing (1041)

Target	Relation	Type	Str
benchmark_ot_ad_answer_key:LRP1	data_in	dataset_row	0.00
ds-6784494f1741	data_in	dataset	1.00
ds-83b31ef18d49	provides_data_for	dataset	1.00
Amyloid-beta	regulates	compound	0.95
Notch Pathway	mediates	pathway	0.95
Notch Pathway Activation	mediates	pathway	0.95
Alzheimer'S Disease	associated_with	disease	0.95
AMYLOID-Β	regulates	entity	0.95
Astrocytes	expressed_in	cell_type	0.90
Amyloid-Beta Metabolism	regulates	process	0.90
Endothelial Cells	expressed_in	cell_type	0.90
Alzheimer's Disease	associated_with	disease	0.90
Notch Signaling Activation	activates	process	0.90
M2-like Macrophage Polarization	upregulates	process	0.90
Delta ligands	mediates_ubiquitination	protein	0.90
Epithelial-Mesenchymal Transition	associated_with	process	0.90
Amyloid-Β Peptides	regulates	molecule	0.90
neuronal ferroptosis	inhibits	process	0.90
DELTA LIGANDS	regulates	protein	0.90
Ubiquitination	mediates	process	0.85
Als	therapeutic_target	disease	0.85
endothelial dysfunction	contributes_to	phenotype	0.85
Late-Onset Alzheimer'S Disease	associated_with	disease	0.85
Alzheimer	therapeutic_target	disease	0.85
DELTA LIGANDS	mediates	protein	0.85
blood-brain barrier integrity	biomarker_for	phenotype	0.85
Anti-PD-1 Resistance	causes	phenotype	0.85
DLL4	upregulates	gene	0.85
Brain Homeostasis	associated_with	process	0.85
amyloid-beta metabolism	modulates	process	0.85
LIPID METABOLISM	regulates	entity	0.85
Microglial Phagocytosis of Amyloid-β	involved_in	process	0.85
BRAIN HOMEOSTASIS	associated_with	entity	0.85
NEURODEGENERATION	associated_with	gene	0.82
neurodegeneration	associated_with	disease	0.82
pulmonary arterial hypertension	associated_with	disease	0.80
RRM1	regulates	gene	0.80
ubiquitin-proteasome	participates_in	pathway	0.80
neurons	expressed_in	cell_type	0.80
Leukemia	targets	disease	0.80
amyloid beta	regulates	protein	0.80
DLL4-NOTCH2-CCL2 axis	modulates	pathway	0.80
NF-κB signaling	activates	pathway	0.80
Blood-Brain Barrier Function	regulates	process	0.80
Pulmonary Arterial Hypertension	associated_with	disease	0.80
apoE	regulates	gene	0.80
mitochondria transfer	promotes	process	0.80
APOE	regulates	gene	0.80
DLL4	regulates	protein	0.80
β-catenin	regulates	protein	0.80

Incoming (614)

Source	Relation	Type	Str
benchmark_ot_ad_answer_key:LRP1	data_in	dataset_row	0.00
ALZHEIMER'S DISEASE	associated_with	gene	1.00
ds-6784494f1741	data_in	dataset	1.00
ds-83b31ef18d49	data_in	dataset	1.00
EPSIN1	regulates	gene	0.90
AMYLOID	associated_with	gene	0.90
SDA-2026-04-02-gap-tau-prop-20260402003221-H001	targets	hypothesis	0.90
EPSIN2	regulates	gene	0.90
h-b948c32c	targets	hypothesis	0.90
h-84808267	targets	hypothesis	0.90
h-7e0b5ade	targets	hypothesis	0.90
APOE	associated_with	gene	0.90
endothelial cells	expressed_in	cell_type	0.90
astrocytes	expressed_in	cell_type	0.90
APOPTOSIS	associated_with	gene	0.82
h-4dd0d19b	targets	hypothesis	0.80
ALZHEIMER DISEASE	associated_with	gene	0.80
UBIQUITIN	regulates	entity	0.75
APP	associated_with	gene	0.74
YBX1	activates	protein	0.72
YBX1	regulates	protein	0.72
APOE	mediates	gene	0.70
ENDOTHELIAL	regulates	cell_type	0.70
GABAERGIC	stabilizes	cell_type	0.70
BIN1	interacts_with	gene	0.70
ENDOTHELIAL	inhibits	cell_type	0.70
ENDOTHELIAL	enhances	cell_type	0.70
ACHE	activates	gene	0.70
ENDOTHELIAL	causes	cell_type	0.70
CCL2	associated_with	gene	0.70
LDLR	regulates	gene	0.70
ENDOTHELIAL	activates	cell_type	0.70
ENDOTHELIAL	interacts_with	cell_type	0.70
ENDOTHELIAL	associated_with	cell_type	0.70
ENDOTHELIAL	expresses	cell_type	0.70
ASTROCYTE	protects_against	cell_type	0.70
GSK3B	interacts_with	gene	0.70
BECN1	interacts_with	gene	0.70
Curli fibrils	binds	protein	0.70
MELATONIN	activates	drug	0.70
SYNAPTIC PLASTICITY	protects_against	phenotype	0.70
ENDOTHELIAL CELLS	regulates	cell_type	0.70
TAU	causes	protein	0.70
APOE	protects_against	gene	0.70
TAU	biomarker_for	protein	0.70
CREB	interacts_with	gene	0.70
CLU	associated_with	gene	0.66
AKT	activates	gene	0.65
DEPRESSION	processes	disease	0.65
DEPRESSION	regulates	disease	0.65

Targeting Hypotheses (12)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
LRP1-Dependent Tau Uptake Disruption	0.808	neurodegeneration	Tau propagation mechanisms and therapeut
Circadian-Synchronized LRP1 Pathway Activation	0.714	neurodegeneration	Blood-brain barrier transport mechanisms
LRP1-Mediated Transcytosis for CNS Antibody Delivery	0.680	neurodegeneration	Blood-brain barrier antibody transport m
LRP1/NLRP3/IL-1β Cascade Links Aβ Endocytosis to Inflammasom	0.617	neurodegeneration	How do perivascular cells specifically r
APOE4 preferentially signals through LRP1 over LDLR, alterin	0.610	neuroscience	APOE4-driven lipid metabolism dysregulat

Astrocyte LRP1-mediated tau uptake and APOE4-dependent secre	0.610	neurodegeneration	Which tau propagation mechanism predomin
LRP1-Dependent Tau Uptake Disruption	0.576	Alzheimer's Disease	Tau propagation mechanisms and therapeut
Blocking Exosomal Tau Uptake at Neuronal LRP1 Receptors Disr	0.570	neurodegeneration	Investigate prion-like spreading of tau
LRP1-mediated synaptic uptake drives early entorhinal-hippoc	0.570	neurodegeneration	Which tau propagation mechanism predomin
LRP1 Loss-of-Function Derepresses P2RY12 Expression	0.500	neurodegeneration	What determines P2RY12 receptor expressi
LRP1-Autophagy BBB Permeabilization for Antibody Transport	0.380	neurodegeneration	Blood-brain barrier antibody transport m
Poorly lipidated APOE4 particles are preferentially routed t	0.340	molecular biology	Does APOE4's reduced lipid-binding direc

Mentioning Analyses (9)

Scientific analyses that reference this entity

Gene Co-expression Network Analysis of AD Progression Modules

neurodegeneration | 2026-04-16 | 0 hypotheses

Do bacterial curli amyloids cross the blood-brain barrier to directly seed α-syn

neurodegeneration | 2026-04-12 | 0 hypotheses

Why do systemic anti-inflammatory drugs fail in AD despite cardiovascular effica

clinical neurology | 2026-04-08 | 0 hypotheses

Investigate prion-like spreading of tau pathology through connected brain region

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

Tau propagation mechanisms and therapeutic interception points

neurodegeneration | 2026-04-04 | 15 hypotheses Top: 0.814

Experiments (10)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
Meta-analysis of LRP1 C766T polymorphism and Alzheimer's disease susce	exploratory	Alzheimer's disease	0.950	human patients	proposed	N/A
Endothelial CD2AP knockdown effects on memory in male mice	validation	Alzheimer's disease	0.900	male mice	proposed	N/A
HDAC4 inhibition and NHE6 expression mechanism study	exploratory	Alzheimer's disease	0.850		proposed	N/A
Network Pharmacology Analysis of Shared AD Targets	exploratory	Alzheimer's disease	0.850	Computational network analysis	proposed	N/A
MRI Phenotyping Method Concordance in Serbian AD Cohort	clinical	Alzheimer's disease	0.850	human patients	proposed	N/A
Endothelin-1 receptor A antagonist rescue in male CD2AP mice	validation	Alzheimer's disease	0.850	male mice	proposed	N/A
Neuroimmune modulation and Aβ clearance mechanisms	exploratory	Alzheimer's disease	0.820	Microglia and astrocytes	proposed	N/A
CD2AP expression and cognitive decline in AD patients	exploratory	Alzheimer's disease	0.800	human patients	proposed	N/A
Bioinformatics analysis and hub gene identification	exploratory	Alzheimer's disease	0.800	computational analysis of tran	proposed	N/A
Competing endogenous RNA (ceRNA) network construction	exploratory	Alzheimer's disease	0.750	computational network analysis	proposed	N/A

Related Papers (20)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
Interplay of Low-Density Lipoprotein Receptors, LRPs, and Lipoproteins in Pulmon [PMID:35257044]	Calvier L, Herz J, Hansmann G	JACC Basic Transl Sci	2022	1
ROS-responsive nanogels for brain targeted delivery of icariin in the treatment [PMID:41197818]	["Li X", "Huang J", "Zhou Y", "Chen X",	International journal of pharm	2026	0
Modulating LRP1 Pathways in Alzheimer's Disease: Mechanistic Insights and Emergi [PMID:41772271]	Mushtaq T, Hameed H, Khan MA, Tariq U, H	Molecular neurobiology	2026	0
Insulin-like growth factor-1 enhances β-amyloid protein clearance in HMC3 microg [PMID:41621577]	Guo H, Peng X, Zhang X, Ruganzu JB, Wu X	Experimental cell research	2026	0
Osteoclast-secreted galectin-3 promotes articular cartilage degeneration in OVX [PMID:40609733]	Chen L, Hong H, Yang Z, Zhong Y, Sun S e	Osteoarthritis Cartilage	2026	0
Small-molecule PCSK9 inhibition enhances BBB amyloid-β clearance and suppresses [PMID:41927877]	Miao J, Wang J, Zhou W, Guo J	Sci Rep	2026	0
Lysosomal trafficking markers covering PSAP, PGRN, SORT1 and LRP1 in body liquid [PMID:41579784]	Poniatowski ŁA, Siwińska A, Acewicz A, K	Forensic science international	2026	0
Mitochondrial calcium uniporter knockdown in hippocampal neurons effectively att [PMID:41687804]	Wu L, Hou F, Wang Z, Wu M, Wang X, Cao J	Experimental neurology	2026	0
Bionanoconjugates in Neurodegeneration: Peptide-Nanoparticle Alliances for Next- [PMID:41199078]	["Ranjitha V", "Kumar A", "Kaalappa P"]	Pharmaceutical research	2025	0
Integrative bioinformatics frameworks for abdominal aortic aneurysm using GWAS m [PMID:40595262]	Sagulkoo P, Chuntakaruk H, Suratanee A,	Scientific reports	2025	0
Inhibition of tau neuronal internalization using anti-tau single domain antibodi [PMID:40175345]	["Danis C", "Dupr\u00e9 E", "Bouillet T"	Nature communications	2025	0
Schwann cell Lrp1 deletion drives trigeminal neuron sensitization and orofacial [PMID:41430102]	Gong Z, Zhang M, Liu N, Asam K, Martellu	The journal of headache and pa	2025	0
Ganglioside sialylation modulates tau internalization and pathology spread. [PMID:41398374]	Li S, Chen Y, Song T, Liu D, Wu R, Yang	Molecular psychiatry	2025	0
Microglia internalize tau monomers and fibrils using distinct receptors but simi [PMID:39713861]	Falkon KF, Danford L, Gutierrez Kuri E,	Alzheimer's & dementia : the j	2025	0
Exosomes as nanocarriers for brain-targeted delivery of therapeutic nucleic acid [PMID:40533746]	["Sanadgol N", "Abedi M", "Hashemzaei M"	Journal of nanobiotechnology	2025	0
Astrocytic LRP1 enables mitochondria transfer to neurons and mitigates brain isc [PMID:38906140]	Zhou J, Zhang L, Peng J, Zhang X, Zhang	Cell metabolism	2024	0
Mitochondrial NADK2-dependent NADPH controls Tau oligomer uptake in human neuron [PMID:39554169]	Pardo E, Kim T, Wallrabe H, Zengeler KE,	bioRxiv : the preprint server	2024	0
The role of neutrophils in tPA thrombolysis after stroke: a malicious troublemak [PMID:39606238]	Li Q, Ye J, Li Z, Xiao Q, Tan S, Hu B, J	Frontiers in immunology	2024	0
Editorial for “Corrected <scp>MRI</scp> Pulmonary Transit Time for Identificatio [PMID:36029232]	Ricci Fabrizio; Khanji Mohammed Y; Garg	Journal of Magnetic Resonance	2023	0
Ancient gene linkages support ctenophores as sister to other animals. [PMID:37198475]	["Schultz D", "Haddock S", "Bredeson J",	Nature	2023	0

Debates (14)

Multi-agent debates referencing this entity

Should metabolic reprogramming via SIRT1/NAD+/PGC-1alpha axis be prioritized to

closed · Rounds: 4 · Score: 0.81 · 2026-04-23

Investigate prion-like spreading of tau pathology through connected brain region

closed · Rounds: 4 · Score: 0.73 · 2026-04-22

What co-expression modules are shared and unique across brain regions in AD, and

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

Is TYROBP a genuine therapeutic target in AD, or is it a downstream marker of mi

closed · Rounds: 4 · Score: 0.70 · 2026-04-16

Investigate the therapeutic potential of clearing senescent cells (senolytics) t

closed · Rounds: 4 · Score: 0.75 · 2026-04-16

Investigate prion-like spreading of tau pathology through connected brain region

closed · Rounds: 4 · Score: 0.90 · 2026-04-12

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

closed · Rounds: 4 · Score: 0.69 · 2026-04-12

Do bacterial curli amyloids cross the blood-brain barrier to directly seed α-syn

closed · Rounds: 4 · Score: 0.84 · 2026-04-12

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

closed · Rounds: 7 · Score: 0.91 · 2026-04-10

The debate noted clinical failures of TNF-α and IL-6 inhibitors in AD despite th

closed · Rounds: 4 · Score: 0.79 · 2026-04-09

Related Research

Hypotheses and analyses mentioning LRP1 in their description or question text

LRP1

Understanding Entity Pages

Summary

Wiki Pages (20)

APOE contributes to Alzheimer's disease by regulating both beta-amyloid deposition

LRP1B — Low Density Lipoprotein Receptor-Related Protein 1B

LRP1-ApoE Signaling Cascade

LRP1-Mediated Amyloid-Beta Clearance in Neurodegeneration

LRP1-Targeted ApoE-Mimetic Peptide Delivery

LRP1-Enhanced Perivascular Drainage Therapy

LRP12 Protein

NLRP1 Inflammasome Modulation Therapy for Neurodegeneration

LRP1B Protein

LRP1 (Low-Density Lipoprotein Receptor-Related Protein 1)

LRP12 — Low Density Lipoprotein Receptor-Related Protein 12

LRP1B Protein - LDL Receptor-Related Protein 1B

LRP1 Gene

NLRP1 Protein

NLRP1 Gene

LRP10 Protein

NLRP12 — NLR Family Pyrin Domain Containing 12

LRP10

NLRP12 Protein — NLR Family Pyrin Domain Containing 12

LRP1 Protein

Pathway Diagram

Outgoing (1041)

Incoming (614)

Targeting Hypotheses (12)

Mentioning Analyses (9)

Gene Co-expression Network Analysis of AD Progression Modules

Do bacterial curli amyloids cross the blood-brain barrier to directly seed α-syn

Why do systemic anti-inflammatory drugs fail in AD despite cardiovascular effica

Investigate prion-like spreading of tau pathology through connected brain region

Tau propagation mechanisms and therapeutic interception points

Senescent cell clearance as neurodegeneration therapy

SEA-AD Gene Expression Profiling — Allen Brain Cell Atlas

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

Blood-brain barrier transport mechanisms for antibody therapeutics

Experiments (10)

Related Papers (20)

Debates (14)

Should metabolic reprogramming via SIRT1/NAD+/PGC-1alpha axis be prioritized to

Investigate prion-like spreading of tau pathology through connected brain region

What co-expression modules are shared and unique across brain regions in AD, and

Is TYROBP a genuine therapeutic target in AD, or is it a downstream marker of mi

Investigate the therapeutic potential of clearing senescent cells (senolytics) t

Investigate prion-like spreading of tau pathology through connected brain region

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

Do bacterial curli amyloids cross the blood-brain barrier to directly seed α-syn

PSP and CBD both involve 4R-tau but produce distinct neuropathological patterns

The debate noted clinical failures of TNF-α and IL-6 inhibitors in AD despite th

Related Research

Astrocyte LRP1-mediated tau uptake and APOE4-dependent secretion creates regiona

LRP1-Dependent Tau Uptake Disruption

Blocking Exosomal Tau Uptake at Neuronal LRP1 Receptors Disrupts Interneuronal P

LRP1-mediated synaptic uptake drives early entorhinal-hippocampal tau propagatio

LRP1 Loss-of-Function Derepresses P2RY12 Expression

LRP1-Autophagy BBB Permeabilization for Antibody Transport

Poorly lipidated APOE4 particles are preferentially routed through LDLR/LRP1 int