{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:38:27Z","timestamp":1791279507050,"version":"4.1.0"},"reference-count":39,"publisher":"Society for Neuroscience","issue":"49","license":[{"start":{"date-parts":[[2014,6,4]],"date-time":"2014-06-04T00:00:00Z","timestamp":1401840000000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2013,12,4]]},"abstract":"<jats:p>Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly population. Accumulation, aggregation, and deposition of amyloid-\u03b2 (A\u03b2) peptides generated through proteolytic cleavage of amyloid precursor protein (APP) are likely initiating events in the pathogenesis of AD. While A\u03b2 production is accelerated in familial AD, increasing evidence indicates that impaired clearance of A\u03b2 is responsible for late-onset AD. Because A\u03b2 is mainly generated in neurons, these cells are predicted to have the highest risk of encountering A\u03b2 among all cell types in the brain. However, it is still unclear whether they are also involved in A\u03b2 clearance. Here we show that receptor-mediated endocytosis in neurons by the low-density lipoprotein receptor-related protein 1 (LRP1) plays a critical role in brain A\u03b2 clearance. LRP1 is known to be an endocytic receptor for multiple ligands including A\u03b2. Conditional knock-out of<jats:italic>Lrp1<\/jats:italic>in mouse forebrain neurons leads to increased brain A\u03b2 levels and exacerbated amyloid plaque deposition selectively in the cortex of amyloid model APP\/PS1 mice without affecting A\u03b2 production.<jats:italic>In vivo<\/jats:italic>microdialysis studies demonstrated that A\u03b2 clearance in brain interstitial fluid is impaired in neuronal<jats:italic>Lrp1<\/jats:italic>knock-out mice. Because the neuronal LRP1-deletion did not affect the mRNA levels of major A\u03b2 degrading enzymes, neprilysin and insulin-degrading enzyme, the disturbed A\u03b2 clearance is likely due to the suppression of LRP1-mediated neuronal A\u03b2 uptake and degradation. Together, our results demonstrate that LRP1 plays an important role in receptor-mediated clearance of A\u03b2 and indicate that neurons not only produce but also clear A\u03b2.<\/jats:p>","DOI":"10.1523\/jneurosci.3487-13.2013","type":"journal-article","created":{"date-parts":[[2013,12,4]],"date-time":"2013-12-04T17:38:33Z","timestamp":1386178713000},"page":"19276-19283","source":"Crossref","is-referenced-by-count":272,"title":["Neuronal Clearance of Amyloid-\u03b2 by Endocytic Receptor LRP1"],"prefix":"10.1523","volume":"33","author":[{"given":"Takahisa","family":"Kanekiyo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John 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