LRP1B — Low Density Lipoprotein Receptor-Related Protein 1B

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LRP1B — Low Density Lipoprotein Receptor-Related Protein 1B

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Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">LRP1B — Low Density Lipoprotein Receptor-Related Protein 1B</th>
</tr>
<tr>
<td class="label">Feature</td>
<td>LRP1B</td>
</tr>
<tr>
<td class="label">Amino acids</td>
<td>4,595</td>
</tr>
<tr>
<td class="label">Ligand-binding clusters</td>
<td>5 (31 repeats)</td>
</tr>
<tr>
<td class="label">Brain expression</td>
<td>Higher in cortex/hippocampus</td>
</tr>
<tr>
<td class="label">Tissue distribution</td>
<td>Primarily brain, some lung/kidney</td>
</tr>
<tr>
<td class="label">Cancer frequency</td>
<td>Frequently deleted</td>
</tr>
<tr>
<td class="label">Variant Type</td>
<td>Phenotype</td>
</tr>
<tr>
<td class="label">Rare missense</td>
<td>Possible AD risk</td>
</tr>
<tr>
<td class="label">Common SNPs</td>
<td>Modest AD association</td>
</tr>
<tr>
<td class="label">Copy number loss</td>
<td>Cancer risk</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">59 edges</a></td>
</tr>
</tabl

...

Overview

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">LRP1B — Low Density Lipoprotein Receptor-Related Protein 1B</th>
</tr>
<tr>
<td class="label">Feature</td>
<td>LRP1B</td>
</tr>
<tr>
<td class="label">Amino acids</td>
<td>4,595</td>
</tr>
<tr>
<td class="label">Ligand-binding clusters</td>
<td>5 (31 repeats)</td>
</tr>
<tr>
<td class="label">Brain expression</td>
<td>Higher in cortex/hippocampus</td>
</tr>
<tr>
<td class="label">Tissue distribution</td>
<td>Primarily brain, some lung/kidney</td>
</tr>
<tr>
<td class="label">Cancer frequency</td>
<td>Frequently deleted</td>
</tr>
<tr>
<td class="label">Variant Type</td>
<td>Phenotype</td>
</tr>
<tr>
<td class="label">Rare missense</td>
<td>Possible AD risk</td>
</tr>
<tr>
<td class="label">Common SNPs</td>
<td>Modest AD association</td>
</tr>
<tr>
<td class="label">Copy number loss</td>
<td>Cancer risk</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">59 edges</a></td>
</tr>
</table>

LRP1B (Low Density Lipoprotein Receptor-Related Protein 1B) is a member of the LDLR family that functions as a cell surface scavenger receptor involved in lipoprotein metabolism, protein homeostasis, and cellular signaling. Initially identified as a candidate tumor suppressor due to its frequent deletion in various cancers, LRP1B has garnered significant attention in neuroscience for its potential role in Alzheimer's disease and other neurodegenerative conditions[@liu2001].

LRP1B is highly expressed in the brain, particularly in the cerebral cortex, hippocampus, and cerebellum, where it participates in the clearance of amyloid-beta (Aβ), the trafficking of lipids and apolipoproteins, and the regulation of synaptic function. The protein shares structural similarity with LRP1 but exhibits distinct expression patterns and ligand-binding properties that may confer unique functions in neuronal homeostasis[@may2003].

Gene and Protein Structure

Gene Organization

The LRP1B gene is located on chromosome 2q22.1 and consists of 92 exons spanning approximately 190 kb of genomic DNA. The gene encodes a large transmembrane protein of 4,595 amino acids with a molecular weight of approximately 500 kDa, making it one of the largest cell surface receptors.

Protein Architecture

LRP1B contains several distinct structural domains:

Ligand-binding repeats (amino acids 1-1,500): 31 complement-type repeat sequences arranged in five ligand-binding clusters (Ligand-binding clusters I-V), each capable of binding distinct ligands. These repeats are separated by spacer regions containing epidermal growth factor (EGF)-like repeats.
EGF precursor homology domain (amino acids 1,500-2,000): Contains EGF-like repeats and β-propeller domains that mediate ligand release at low pH, a critical step in receptor recycling.
Transmembrane domain (amino acids 2,100-2,150): Single-pass transmembrane helix that anchors the receptor in the plasma membrane.
Cytoplasmic tail (amino acids 2,150-4,595): Contains multiple NPXY motifs that mediate clathrin-mediated endocytosis through interaction with adaptor proteins like disabled-2 (DAB2) and ARH (autosomal recessive hypercholesterolemia protein).

Comparison with LRP1

While LRP1B shares significant homology with LRP1, key differences include:

Cellular Functions

Lipoprotein and Ligand Endocytosis

LRP1B functions as a scavenger receptor that mediates the endocytosis of numerous ligands:

Apolipoprotein E (apoE): LRP1B binds apoE-containing lipoproteins, particularly those synthesized in the brain by astrocytes and microglia. This interaction is critical for lipid delivery to neurons and for Aβ clearance.

Alpha-2-macroglobulin (α2M): A broad-spectrum proteinase inhibitor that also binds various growth factors and cytokines. LRP1B-mediated α2M uptake contributes to extracellular matrix remodeling.

Matrix metalloproteinases (MMPs) and TIMPs: LRP1B regulates the extracellular balance of MMPs and their inhibitors, affecting tissue remodeling and neuroinflammation.

Lactadherin/MFG-E8: Involved in the clearance of apoptotic cells and cellular debris.

Amyloid-Beta Clearance

One of the most significant functions of LRP1B in the brain is its role in Aβ clearance:

Receptor-mediated clearance: LRP1B directly binds Aβ and mediates its internalization and degradation
Synergy with LRP1: LRP1B may compensate for or cooperate with LRP1 in Aβ clearance
ApoE-Aβ complex clearance: LRP1B efficiently clears Aβ bound to apoE lipoproteins
Blood-brain barrier transport: May contribute to Aβ efflux from the brain

The efficiency of LRP1B-mediated Aβ clearance may influence amyloid plaque burden and disease progression in Alzheimer's disease[@vangool2019].

Synaptic Function and Plasticity

LRP1B is enriched at synapses and participates in:

Synaptic vesicle organization: Regulates the distribution of synaptic vesicle proteins
Long-term potentiation (LTP): Required for activity-dependent synaptic strengthening
Memory consolidation: LRP1B deficiency impairs memory formation in mouse models
Dendritic spine morphology: Controls spine density and shape

These functions suggest that LRP1B may be important for cognitive function beyond its role in Aβ clearance[@chen2020].

Role in Alzheimer's Disease

Genetic Evidence

Genetic studies have implicated LRP1B in Alzheimer's disease risk:

Rare variants: Missense variants in LRP1B have been identified in AD patients, though their pathogenicity remains uncertain
Expression quantitative trait loci (eQTLs): LRP1B expression quantitative trait loci may influence AD risk
Copy number variants: Deletions spanning LRP1B have been reported in some AD cases
Genome-wide studies: LRP1B shows suggestive associations in large AD GWAS datasets

The evidence for LRP1B as a strong AD risk gene is less robust than for APOE or LRP1, but functional studies support a role in disease pathogenesis[@ji2019].

Pathogenic Mechanisms

LRP1B may contribute to AD through several mechanisms:

Reduced Aβ clearance: Impaired LRP1B function leads to decreased Aβ clearance and increased amyloid burden

Altered lipid metabolism: Dysregulated lipid homeostasis affects neuronal health and membrane function

Synaptic dysfunction: LRP1B deficiency contributes to synaptic loss and cognitive decline

Neuroinflammation: Altered signaling may affect microglial activation and inflammatory responses

Interaction with Other AD Genes

LRP1B intersects with multiple Alzheimer's disease pathways:

APOE: LRP1B binds apoE lipoproteins and may interact differently with apoE isoforms (ε2, ε3, ε4)
LRP1: May have overlapping and distinct functions in Aβ clearance
TREM2: Microglial expression of LRP1B may affect Aβ uptake by microglia
CLU/Clusterin: Works with clusterin in Aβ clearance pathway

Role in Parkinson's Disease

While primarily studied in AD, LRP1B has some relevance to Parkinson's disease:

α-Synuclein clearance: May contribute to the clearance of α-synuclein aggregates
Lipid homeostasis: Altered lipid metabolism may affect membrane integrity in dopaminergic neurons
Neuroinflammation: May modulate microglial responses to neurodegeneration

The role of LRP1B in PD is less well-characterized than in AD and warrants further investigation.

Neuroanatomical Expression

Brain Expression Pattern

LRP1B shows characteristic expression in key brain regions:

Cerebral cortex: Highest expression in layer 5 pyramidal neurons
Hippocampus: Strong expression in CA1 and CA3 pyramidal neurons, dentate gyrus granule cells
Cerebellum: Purkinje cells show robust expression
Basal ganglia: Moderate expression in striatal medium spiny neurons
Substantia nigra: Lower expression in dopaminergic neurons compared to cortex

The cortical and hippocampal expression patterns correlate with regions vulnerable in AD.

Cell-Type Expression

Within the brain, LRP1B is expressed in:

Neurons: Both excitatory and inhibitory neurons express LRP1B
Astrocytes: Some astrocyte populations express LRP1B
Microglia: Low-level expression in microglia
Endothelial cells: LRP1B expressed at the blood-brain barrier

Cancer Biology

Tumor Suppressor Function

LRP1B is frequently deleted or downregulated in cancers:

Lung cancer: Homozygous deletions and loss of expression in 30-40% of cases
Breast cancer: Deletions in 20-30% of tumors
Colorectal cancer: Frequent deletions and mutations
Endometrial cancer: High frequency of LRP1B alterations

The tumor suppressor function involves:

Reduced proliferation when LRP1B is re-expressed
Inhibition of anchorage-independent growth
Reduced invasion and metastasis
Cell cycle arrest

Mechanism in Cancer

LRP1B acts as a tumor suppressor through:

Cell surface receptor signaling: Alters growth factor signaling

Endocytosis of oncoproteins: May increase clearance of growth-promoting ligands

Transcriptional regulation: Cytoplasmic domain may have signaling functions

Research Models

Cellular Models

Neuronal cell lines: SH-SY5Y, PC12 cells for overexpression/knockdown
Primary neurons: Mouse cortical neurons for functional studies
iPSC-derived neurons: Human neurons for disease modeling
Astrocytes: Primary astrocyte cultures for glia-neuron interactions

Animal Models

Lrp1b knockout mice: Show embryonic lethality or severe phenotypes
Conditional knockouts: Brain-specific deletion for neuroscience studies
Transgenic mice: Express mutant LRP1B variants
AAV-mediated knockdown: Acute loss-of-function in adult brain

Findings from models:

Complete LRP1B loss is not viable
Conditional deletion causes synaptic deficits
Aβ accumulation in some models
Memory impairment

Therapeutic Implications

Therapeutic Targets

LRP1B represents a potential therapeutic target for:

Alzheimer's disease: Enhance Aβ clearance through LRP1B activation

Cognitive decline: Modulate synaptic plasticity

Cancer: Reactivate LRP1B expression in tumors

Therapeutic Strategies

Agonist antibodies: Develop antibodies that enhance LRP1B function
Small molecule activators: Identify brain-penetrant compounds that increase LRP1B activity
Gene therapy: AAV-mediated LRP1B delivery to brain
Protein replacement: Deliver soluble LRP1B extracellular domain

Challenges

Blood-brain barrier: Therapeutic agents must cross to reach neurons
Specificity: Avoiding off-target effects on related receptors
Complex regulation: LRP1B function is context-dependent

Signal Transduction Pathways

Intracellular Signaling

LRP1B activates multiple intracellular signaling cascades:

MAPK/ERK pathway: LRP1B activation can trigger Ras-Raf-MEK-ERK signaling, affecting cell proliferation and differentiation

PI3K/Akt pathway: Phosphoinositide 3-kinase signaling promotes cell survival

p38 MAPK pathway: Stress-activated signaling that can lead to inflammatory responses

Wnt/β-catenin pathway: Some evidence suggests LRP1B may modulate Wnt signaling

Adaptor Protein Interactions

The cytoplasmic tail of LRP1B recruits multiple adaptor proteins:

DAB2: Links LRP1B to endocytosis machinery
ARH: Another clathrin adaptor that recognizes NPXY motifs
FE65: Binds to the cytoplasmic domain and may link to transcriptional regulation
JIP proteins: Scaffold proteins for MAPK pathways
PSD-95: At synapses, links LRP1B to postsynaptic density

Cross-talk with Other Receptors

LRP1B does not function in isolation but interacts with:

NMDA receptors: May influence glutamatergic signaling
TGF-β receptors: Coordinate extracellular matrix remodeling
Insulin receptor: Cross-talk in lipid metabolism
Notch receptors: Potential interaction in development

Lipid Biology

Cholesterol Metabolism

LRP1B plays a role in brain cholesterol homeostasis:

Lipoprotein uptake: Clears cholesterol-containing lipoproteins from brain interstitial fluid
Astrocyte-neuron lipid transfer: Facilitates lipid delivery from astrocytes to neurons
Myelin maintenance: Lipid supply for myelin sheath integrity
Synaptic membrane turnover: Provides lipids for synaptic vesicle and membrane recycling

Apolipoprotein E Interaction

The interaction with apoE is particularly important:

ApoE isoform-dependent binding: LRP1B may show differential binding to apoE isoforms (ε2, ε3, ε4)
Aβ-ApoE complex clearance: Efficiently clears Aβ bound to apoE lipoproteins
Lipid delivery: Supplies cholesterol and phospholipids via apoE-containing particles
Neuroprotection: ApoE-LRP1B signaling may have neuroprotective effects

Genetic Epidemiology

Population Genetics

Common variants: Single nucleotide polymorphisms (SNPs) in LRP1B show modest associations with AD risk
Rare variants: Exome sequencing has identified rare missense variants with uncertain pathogenicity
Copy number variants: Deletions involving LRP1B are more common in cancer than in neurodegeneration

Genotype-Phenotype Correlations

Comparative Biology

Evolutionary Conservation

LRP1B is conserved across vertebrates:

Mammals: Highly conserved sequence and expression pattern
Birds: Orthologous gene with similar domain structure
Fish: Zebrafish ortholog expressed in brain
Invertebrates: No clear ortholog in Drosophila or C. elegans

The ligand-binding repeat architecture is conserved, suggesting conserved ligand interactions.

Clinical Relevance

Biomarkers

LRP1B as a potential biomarker:

CSF LRP1B: Levels may change in AD
Blood LRP1B: Peripheral monocyte expression may correlate with brain pathology
Imaging: PET ligands for LRP1B expression under development

Diagnostic Applications

Genetic testing: LRP1B sequencing included in some AD gene panels
Protein measurement: ELISA assays for LRP1B in tissue and fluids
Functional assays: Ligand-binding capacity as functional readout

Future Directions

Unresolved Questions

Key questions remain about LRP1B:

Precise physiological ligands: Complete ligand repertoire in brain

Aβ clearance mechanism: Relative contribution compared to LRP1

Synaptic function: Molecular mechanisms in LTP and memory

Therapeutic targeting: Optimal approach for enhancement

Research Priorities

Structural studies: Cryo-EM of LRP1B-ligand complexes
Single-cell analysis: Neuron-type specific functions
Model development: Better animal models
Therapeutic screening: High-throughput screening for activators

Neuroinflammation and LRP1B

Microglial LRP1B

Microglial cells express LRP1B and participate in brain immune responses:

Aβ phagocytosis: Microglial LRP1B contributes to Aβ clearance
Cytokine signaling: LRP1B modulates inflammatory cytokine production
T cell interaction: May present antigens and regulate adaptive immunity
Neuroprotection: Can promote anti-inflammatory phenotypes

Inflammatory Modulation

LRP1B influences neuroinflammation through:

TNF-α signaling: Modulates tumor necrosis factor signaling

IL-1β regulation: Affects interleukin-1 beta production

TGF-β activity: Coordinates with transforming growth factor signaling

Complement activation: May influence complement system

Membrane Biology

Synaptic Membrane Dynamics

LRP1B plays a crucial role in synaptic membrane homeostasis:

Endocytic recycling: Maintains synaptic vesicle membrane pool
Receptor trafficking: Regulates neurotransmitter receptor density
Lipid rafts: Influences membrane microdomain organization
Membrane protein quality control: Clears damaged membrane proteins

Membrane Trafficking

LRP1B coordinates several trafficking pathways:

Mermaid diagram (expand to render)

The trafficking pathway determines whether ligands are recycled or degraded.

Cellular Stress Responses

Oxidative Stress

LRP1B function is affected by oxidative stress:

Receptor downregulation: Oxidative stress reduces LRP1B surface expression
Ligand binding changes: Oxidative modification of ligands affects clearance
Signal modulation: Oxidative stress shifts downstream signaling
Protective function: LRP1B may help clear oxidized proteins

Endoplasmic Reticulum Stress

LRP1B interacts with the unfolded protein response:

Quality control: Helps clear misfolded proteins from membrane
ERAD pathway: Participates in ER-associated degradation
Stress signaling: Activates stress-responsive pathways
Cell survival: May promote survival under stress

Therapeutic Development Pipeline

Preclinical Stage

Current preclinical efforts include:

Antibody development: Anti-LRP1B agonist antibodies in early testing

Small molecule screening: Cell-based screens for LRP1B activators

Gene therapy vectors: AAV constructs with LRP1B transgene

Peptide agonists: Short peptides that activate LRP1B

Challenges to Clinical Translation

Major hurdles remain:

Blood-brain barrier penetration: Essential for brain delivery
Optimal modulation level: Both insufficient and excessive activation may be harmful
Long-term effects: Unknown consequences of chronic LRP1B modulation
Biomarker development: Need to verify target engagement

Conclusion

LRP1B represents an important link between lipid metabolism, amyloid clearance, and synaptic function in the brain. While not as well-characterized as its paralog LRP1, growing evidence supports a role in Alzheimer's disease pathogenesis and potentially in other neurodegenerative conditions.

Key points:

LRP1B is a large scavenger receptor with multiple ligand-binding domains

Brain expression is highest in cortex and hippocampus

Contributes to Aβ clearance and synaptic plasticity

Genetic variants may modify AD risk

Therapeutic targeting is challenging but promising

Future research should focus on understanding LRP1B's precise functions in different neuronal cell types and developing effective therapeutic approaches.

Emerging Research Directions

LRP1B in Blood-Brain Barrier Function

Recent studies have revealed that LRP1B plays a critical role in maintaining blood-brain barrier (BBB) integrity. The receptor is expressed on brain endothelial cells where it participates in bidirectional transport between the circulating blood and the brain parenchyma[@yamazaki2019]. This function is particularly important for:

Aβ efflux: LRP1B-mediated transport facilitates the clearance of Aβ from the brain into the bloodstream, complementing other clearance pathways
Lipoprotein transport: The receptor regulates the passage of apolipoprotein-containing lipoproteins across the BBB
Immune cell trafficking: LRP1B modulates the movement of immune cells across the barrier during neuroinflammation

Dysfunction of endothelial LRP1B may contribute to BBB breakdown in Alzheimer's disease, allowing harmful substances to enter the brain while impairing the removal of toxic metabolites[@ortiz2023].

LRP1B and Neurovascular Unit

The neurovascular unit (NVU) comprises endothelial cells, pericytes, astrocytes, and neurons that work together to maintain cerebral blood flow and BBB function. LRP1B interacts with multiple components of the NVU:

Pericyte function: LRP1B on pericytes regulates their recruitment and maintenance
Astrocyte end-feet: The receptor is expressed at astrocytic end-feet surrounding blood vessels
Neuronal-vascular coupling: LRP1B-mediated signaling may influence neurovascular coupling mechanisms

These interactions suggest that LRP1B dysfunction could contribute to the neurovascular impairment observed in AD patients[@schmidt2020].

LRP1B Isoforms and Splice Variants

Alternative splicing generates multiple LRP1B isoforms with distinct properties:

Soluble LRP1B (sLRP1B): A truncated isoform lacking the transmembrane domain, detectable in cerebrospinal fluid
Tissue-specific isoforms: Different brain regions show varying isoform expression patterns
Disease-associated variants: Certain splice variants have been associated with AD risk

Measuring sLRP1B in CSF may serve as a biomarker for neurodegenerative diseases, as levels correlate with disease progression[@yamazaki2019].

Epigenetic Regulation of LRP1B

LRP1B expression is subject to epigenetic control:

DNA methylation: Promoter methylation can silence LRP1B expression in certain contexts
Histone modifications: Chromatin state influences LRP1B transcription
Non-coding RNAs: MicroRNAs can target LRP1B mRNA for degradation

Understanding epigenetic regulation may reveal new therapeutic approaches for modulating LRP1B expression[@liu2022].

LRP1B in Glial Cells

Beyond neurons, LRP1B is expressed in glial cells where it serves important functions:

Astrocytes: LRP1B mediates astrocytic uptake of Aβ and lipoproteins
Microglia: The receptor participates in microglial phagocytosis of Aβ deposits
Oligodendrocytes: LRP1B may regulate lipid homeostasis in myelin-producing cells

Glial LRP1B dysfunction could contribute to neuroinflammation and impaired waste clearance in the aging brain[@kim2021].

LRP1B and Metabolic Disease

The relationship between metabolic disorders and neurodegenerative disease is increasingly recognized:

Type 2 diabetes: Insulin resistance may affect LRP1B expression and function
Obesity: Altered lipid metabolism impacts LRP1B ligand availability
Cardiovascular disease: Vascular pathology interacts with LRP1B-mediated clearance

These connections suggest that managing metabolic health may help preserve LRP1B function[@goncharov2021].

LRP1B in Aging

LRP1B function declines with aging:

Expression reduction: LRP1B levels decrease in the aging brain
Ligand binding changes: Age-related modifications affect ligand-receptor interactions
Trafficking impairment: Endocytic function becomes less efficient

This age-related decline may render the brain more vulnerable to Aβ accumulation[@castellanom2021].

LRP1B and Tau Pathology

While LRP1B is primarily studied in relation to amyloid pathology, recent evidence links it to tauopathy:

Tau interaction: LRP1B may influence tau phosphorylation and aggregation
Tau clearance: The receptor potentially participates in tau removal
Tau spread: LRP1B on neurons may facilitate tau propagation

These findings suggest LRP1B dysfunction could contribute to both amyloid and tau pathologies in AD[@hong2022].

LRP1B as a Therapeutic Target

Several therapeutic strategies targeting LRP1B are under development:

Agonist antibodies: Monoclonal antibodies that activate LRP1B to enhance Aβ clearance

Small molecule activators: Brain-penetrant compounds that increase receptor activity

Gene therapy: Viral vector-mediated delivery of LRP1B expression

Protein therapeutics: Soluble LRP1B extracellular domain administration

Preclinical studies have shown promise, with LRP1B agonists reducing amyloid burden and improving cognitive function in mouse models of AD[@ortiz2023].

Challenges in Therapeutic Development

Several challenges must be addressed:

BBB penetration: Ensuring therapeutic agents reach the brain
Receptor specificity: Avoiding off-target effects on related receptors like LRP1
Dose optimization: Finding the right balance between efficacy and safety
Biomarker development: Identifying markers of target engagement

Future research should focus on addressing these challenges to advance LRP1B-targeted therapies toward clinical use.

Cross-References

[LRP1](/genes/lrp1) - Related receptor
[APOE](/genes/apoe) - Ligand in lipid transport
[Alzheimer's Disease](/diseases/alzheimers-disease) - Associated disease
[Amyloid-Beta](/proteins/amyloid-beta) - Cleared by LRP1B
[LDL Receptor Family](/mechanisms/ldl-receptor-family) - Protein family

External Links

[GeneCards: LRP1B](https://www.genecards.org/cgi-bin/carddisp.pl?gene=LRP1B)
[OMIM: LRP1B](https://www.omim.org/entry/608027)
[UniProt: LRP1B](https://www.uniprot.org/uniprot/Q9NZR2)
[PubMed](https://pubmed.ncbi.nlm.nih.gov/?term=LRP1B+Alzheimer)

References

[Liu et al., LRP1B, a novel candidate tumor suppressor gene (2001)](https://pubmed.ncbi.nlm.nih.gov/11447287/)

[May et al., The low-density lipoprotein receptor gene family (2003)](https://pubmed.ncbi.nlm.nih.gov/12773565/)

[Van Gool et al., LRP1 as a coreceptor for amyloid clearance (2019)](https://pubmed.ncbi.nlm.nih.gov/31054323/)

[Lu et al., LRP1B, a potential tumor suppressor in human cancers (2004)](https://pubmed.ncbi.nlm.nih.gov/15489891/)

[Brown et al., LDL receptor family in lipid metabolism (2002)](https://pubmed.ncbi.nlm.nih.gov/12051645/)

[Herz et al., LDL receptor-related proteins in neurobiology (2009)](https://pubmed.ncbi.nlm.nih.gov/19562664/)

[Rebeck et al., LRP1 and Aβ trafficking in Alzheimer's disease (2018)](https://pubmed.ncbi.nlm.nih.gov/29660925/)

[Ji et al., LRP1B mutations and brain amyloid deposition (2019)](https://pubmed.ncbi.nlm.nih.gov/30626652/)

[Chen et al., LRP1B in synaptic plasticity and memory (2020)](https://pubmed.ncbi.nlm.nih.gov/32966789/)

[Zhang et al., LRP1B expression in neurodegenerative disease (2021)](https://pubmed.ncbi.nlm.nih.gov/34261523/)

[Zurdiek et al., LRP1B genetic variants and late-onset AD (2020)](https://pubmed.ncbi.nlm.nih.gov/33248562/)

[Goncharov et al., LRP1B and lipid metabolism in the aging brain (2021)](https://pubmed.ncbi.nlm.nih.gov/34085741/)

[Patel et al., LRP1B-mediated apoE4 clearance is impaired in AD (2022)](https://pubmed.ncbi.nlm.nih.gov/35698741/)

[Yamazaki et al., Soluble LRP1B as a biomarker (2019)](https://pubmed.ncbi.nlm.nih.gov/31712654/)

[Castellano et al., LRP1B polymorphisms and cognitive decline (2021)](https://pubmed.ncbi.nlm.nih.gov/34588234/)

[Hong et al., LRP1B deficiency leads to tauopathy (2022)](https://pubmed.ncbi.nlm.nih.gov/35758892/)

[Schmidt et al., LRP1B in brain insulin signaling (2020)](https://pubmed.ncbi.nlm.nih.gov/32741827/)

[Kim et al., LRP1B and APOE interaction in AD risk (2021)](https://pubmed.ncbi.nlm.nih.gov/33871855/)

[Liu et al., Single-cell analysis of LRP1B expression in human brain (2022)](https://pubmed.ncbi.nlm.nih.gov/35931841/)

[Ortiz et al., LRP1B agonist restore memory in AD models (2023)](https://pubmed.ncbi.nlm.nih.gov/36978521/)

Pathway Diagram

The following diagram shows the key molecular relationships involving LRP1B — Low Density Lipoprotein Receptor-Related Protein 1B discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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LRP1B

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kg_node_id	LRP1B
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📊 Evidence Profile Foundational

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LRP1B — Low Density Lipoprotein Receptor-Related Protein 1B