Modulating LRP1 Pathways in Alzheimer's Disease: Mechanistic Insights and Emerging Therapies - PubMed

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Alzheimer's disease (AD) is the leading cause of dementia globally, characterized by amyloid β (Aβ) accumulation, tau hyperphosphorylation, and neuroinflammation.
Low-density lipoprotein receptor-related protein 1 (LRP1) is a promising therapeutic target due to its role in Aβ efflux, tau control, and neurovascular maintenance.
LRP1 deficiency in AD worsens clearance, vascular impairment, and neurodegeneration.
Emerging therapies include ligand-functionalized nanocarriers, antibodies, gene manipulation, and strategies like upregulating hepatic LRP1 or modulating cofactors like ANKS1A.
Challenges include lower receptor expression, systemic off-target effects, and blood-brain barrier (BBB) penetration.
Innovative approaches include engineered nanoparticles, ApoE4 interaction prevention, and endothelial-targeted gene therapy.
LRP1 modulation is repositioned as a multifaceted therapeutic gateway for AD.

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