Elimination of amyloid-β peptide (Aβ) from the brain is poorly understood. After intracerebral microinjections in young mice, 125I-Aβ1-40 was rapidly removed from the brain (t1/2 ≤ 25 minutes), mainly by vascular transport across the blood-brain barrier (BBB). The efflux transport system for Aβ1-40 at the BBB was half saturated at 15.3 nM, and the maximal transport capacity was reached between 70 nM and 100 nM. Aβ1-40 clearance was substantially inhibited by the receptor-associated protein, and by antibodies against LDL receptor–related protein-1 (LRP-1) and α2-macroglobulin (α2M). As compared to adult wild-type mice, clearance was significantly reduced in young and old apolipoprotein E (apoE) knockout mice, and in old wild-type mice. There was no evidence that Aβ was metabolized in brain interstitial fluid and degraded to smaller peptide fragments and amino acids before its transport across the BBB into the circulation. LRP-1, although abundant in brain microvessels in young mice, was downregulated in older animals, and this downregulation correlated with regional Aβ accumulation in brains of Alzheimer’s disease (AD) patients. We conclude that the BBB removes Aβ from the brain largely via age-dependent, LRP-1–mediated transport that is influenced by α2M and/or apoE, and may be impaired in AD.
Masayoshi Shibata, Shinya Yamada, S. Ram Kumar, Miguel Calero, James Bading, Blas Frangione, David M. Holtzman, Carol A. Miller, Dudley K. Strickland, Jorge Ghiso, Berislav V. Zlokovic
Usage data is cumulative from December 2018 through December 2019.
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.