ArticleProceedings of the National Academy of Sciences of the United States of America1996
Glycoprotein 330/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
161 citing papers in PubMed, 2 syntheses or guidelines pooled it, 428 citations in OpenAlex.
- The Role of Clusterin Transporter in the Pathogenesis of Alzheimer's Disease at the Blood-Brain Barrier Interface: A Systematic Review.Biomolecules · 2022Pooled it
- Genetic variation in clusterin and risk of dementia and ischemic vascular disease in the general population: cohort studies and meta-analyses of 362,338 individuals.BMC medicine · 2018Pooled it
- Replication of CLU, CR1, and PICALM associations with alzheimer disease.Archives of neurology · 2010Trial
- Clusterin is enriched in plaque-associated astrocytes and localizes to synapses in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Diurnal choroid plexus function in mice depends on sex, age, and amyloid-β status.Communications biology · 2026Article
- The association of Alzheimer's disease-related SNPs with mild cognitive impairment susceptibility in the Chinese population.Scientific reports · 2026Article
- Development of a Novel Immunoprecipitation Method for Extracting Monoclonal Antibodies From Brain Tissue and Its Application to Assessing In Vivo Brain Penetration in Mouse via Liquid Chromatography-Mass Spectrometry.Biomedical chromatography : BMC · 2025Article
- Cerebral Amyloid Deposition WithHuman brain mapping · 2025Article
- Clusterin Regulates the Mechanisms of Neuroinflammation and Neuronal Circuit Impairment in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Article
- Clusterin from endometrial glands plays a critical role in decidualization via Trem2.BMC genomics · 2024Article
- Clusterin is a Potential Therapeutic Target in Alzheimer's Disease.Molecular neurobiology · 2024Review
- Cryo-EM structures elucidate the multiligand receptor nature of megalin.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Discovery of plasma biomarkers related to blood-brain barrier dysregulation in Alzheimer's disease.Frontiers in bioinformatics · 2024Article
- Blood-brain barrier integrity impacts the use of plasma amyloid-β as a proxy of brain amyloid-β pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- An association of CSF apolipoprotein E glycosylation and amyloid-beta 42 in individuals who carry the APOE4 allele.Alzheimer's research & therapy · 2023Article
- Article
- Plasma high-density lipoprotein cargo is altered in Alzheimer's disease and is associated with regional brain volume.Journal of neurochemistry · 2022Article
- Isotopic N,N-dimethyl leucine tags for absolute quantification of clusterin and apolipoprotein E in Alzheimer's disease.Journal of proteomics · 2022Article
101 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
A soluble form of Alzheimer disease amyloid beta-protein (sA beta) is transported in the blood and cerebrospinal fluid mainly complexed with apolipoprotein J (apoJ). Using a well-characterized in situ perfused guinea pig brain model, we recently obtained preliminary evidence that apoJ facilitates transport of sA beta (1-40)-apoJ complexes across the blood-brain barrier and the blood-cerebrospinal fluid barrier, but the mechanisms remain poorly understood. In the present study, we examined the transport process in greater detail and investigated the possible role of glycoprotein 330 (gp330)/megalin, a receptor for multiple ligands, including apoJ. High-affinity transport systems with a Km of 0.2 and 0.5 nM were demonstrated for apoJ at the blood-brain barrier and the choroid epithelium in vivo, suggesting a specific receptor-mediated mechanism. The sA beta (1-40)-apoJ complex shared the same transport mechanism and exhibited 2.4- to 10.2-fold higher affinity than apoJ itself. Binding to microvessels, transport into brain parenchyma, and choroidal uptake of both apoJ and sA beta (1-40)-apoJ complexes were markedly inhibited (74-99%) in the presence of a monoclonal antibody to gp330/megalin and were virtually abolished by perfusion with the receptor-associated protein, which blocks binding of all known ligands to gp330. Western blot analysis of cerebral microvessels with the monoclonal antibody to gp330 revealed a protein with a mass identical to that in extracts of kidney membranes enriched with gp330/megalin, but in much lower concentration. The findings suggest that gp330/megalin mediates cellular uptake and transport of apoJ and sA beta (1-40)-apoJ complex at the cerebral vascular endothelium and choroid epithelium.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.