{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T01:46:20Z","timestamp":1793843180634,"version":"4.6.1"},"reference-count":197,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Alzheimer\u2019s 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 (A\u03b2) is suggested to play a pivotal role in the pathogenesis of AD, and enhancing the clearance of A\u03b2 from the brain has emerged as a major research direction. As the primary receptor for A\u03b2 clearance at the blood-brain barrier (BBB), low-density lipoprotein receptor-related protein 1 (LRP1) plays a crucial role in regulating A\u03b2 transport and metabolism. Understanding the mechanisms through which LRP1 functions, as well as the factors that influence its activity is essential for enhancing A\u03b2 clearance from the brain and developing targeted therapeutic strategies for Alzheimer\u2019s disease. In this review, we introduce the transport of A\u03b2 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 A\u03b2 dynamics and a clinically actionable target for treatment of Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3389\/fnagi.2025.1669405","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:38:12Z","timestamp":1767940692000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["LRP1 at the crossroads of A\u03b2 clearance and therapeutic targeting in Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuepeng","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haolin","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Lan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxiong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanfang","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohe","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyong","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1089\/neu.2023.0284","article-title":"Exposure to low-intensity blast increases clearance of brain amyloid Beta","volume":"41","author":"Abutarboush","year":"2024","journal-title":"J. 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