LRP1 at the crossroads of Aβ clearance and therapeutic targeting in Alzheimer’s disease

TL;DR

This paper reviews how LRP1 helps clear amyloid-beta in Alzheimer’s disease and its potential as a therapeutic target.

Contribution

The paper provides a comprehensive review of LRP1’s role in Aβ clearance and its therapeutic potential in Alzheimer’s disease.

Findings

LRP1 is the primary receptor for Aβ clearance at the blood-brain barrier.

Factors influencing LRP1 activity are critical for developing Alzheimer’s therapies.

LRP1 is a promising therapeutic target for enhancing Aβ clearance in AD.

Abstract

Alzheimer’s disease (AD), characterized by progressive cognitive decline, memory impairment and behavioral disturbances, is the most common form of dementia, and no disease-modifying treatments are available to halt or slow its progression. Amyloid-beta (Aβ) is suggested to play a pivotal role in the pathogenesis of AD, and enhancing the clearance of Aβ from the brain has emerged as a major research direction. As the primary receptor for Aβ clearance at the blood-brain barrier (BBB), low-density lipoprotein receptor-related protein 1 (LRP1) plays a crucial role in regulating Aβ transport and metabolism. Understanding the mechanisms through which LRP1 functions, as well as the factors that influence its activity is essential for enhancing Aβ clearance from the brain and developing targeted therapeutic strategies for Alzheimer’s disease. In this review, we introduce the transport of Aβ across the BBB, followed by a discussion of the basic structure and function of LRP1 and its role in AD progression. Then, we summarize factors affecting LRP1 function and current advances in LRP1-targeted therapies. Finally, we explore the potential of LRP1 as a therapeutic target for AD. So, LRP1 may be a central modulator of Aβ dynamics and a clinically actionable target for treatment of Alzheimer’s disease.

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