ArticleCellular and molecular life sciences : CMLS2022
PCSK9 acts as a key regulator of Aβ clearance across the blood-brain barrier.
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Restores Aβ Clearance by Overcoming PCSK9-LRP1 Dysregulation and TRIB3-Mediated Autophagy Blockade in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- PCSK9 inhibitors in neurodegenerative disorders: mechanisms, therapeutic potential, and clinical implications.Translational neurodegeneration · 2026Review
- Transport pathways across the blood-brain barrier for waste clearance and drug delivery.Fluids and barriers of the CNS · 2026Review
- Circulatory pro-CTSD binds brain endothelial LRP1 to trigger its lysosomal degradation leading to amyloid beta clearance deficit in Alzheimer's disease mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Small-molecule PCSK9 inhibition enhances BBB amyloid-β clearance and suppresses microglial inflammation in Alzheimer's disease models.Scientific reports · 2026Article
- Blood PCSK9 Impacts Alzheimer's Disease Risk in anHealth science reports · 2026Article
- Mechanisms, Mediators, and Pharmacological Approaches Targeting Brain Cholesterol Transport in Alzheimer's Disease.Current pharmaceutical design · 2026Review
- A narrative review of PCSK9 inhibitors: from evolocumab to novel discoveries.Frontiers in pharmacology · 2026Review
- Metabolic cell death networks in Alzheimer's disease: mechanistic links and therapeutic perspectives of ferroptosis, cuproptosis, and disulfidptosis.Frontiers in cell and developmental biology · 2026Review
- The Roles of PCSK9 in Alzheimer's Disease: A Systematic Review of Clinical, Genetic, and Preclinical Evidence.Life (Basel, Switzerland) · 2025Review
- Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.Nature aging · 2025Article
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Alzheimer's Disease: Recent Advances and Controversies.Molecular neurobiology · 2025Review
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9): The Multifaceted Biology, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- Targeting the awry Aβ pathway in Alzheimer's disease: hype and hurdles.Inflammopharmacology · 2025Review
- Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach.European journal of medical research · 2025Review
- Cholesterol-modifying strategies for Alzheimer disease: promise or fallacy?Expert review of neurotherapeutics · 2025Review
- The Cross-Talk Between the Peripheral and Brain Cholesterol Metabolisms.Current issues in molecular biology · 2025Review
- Systemic lipid and glucose modulation differentially affects cognitive function and neuroinflammation in a mouse model of Alzheimer's disease.Frontiers in neuroscience · 2025Article
- A Novel Perspective on PCSK9 in Alzheimer's Disease: A Focus on Amyloid Beta.Current medicinal chemistry · 2025Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Despite the neurodegenerative disorder Alzheimer's disease (AD) is the most common form of dementia in late adult life, there is currently no therapy available to prevent the onset or slow down the progression of AD. The progressive cognitive decline in AD correlates with a successive accumulation of cerebral amyloid-β (Aβ) due to impaired clearance mechanisms. A significant percentage is removed by low-density lipoprotein receptor-related protein 1 (LRP1)-mediated transport across the blood-brain barrier (BBB) into the periphery. Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to members of the low-density lipoprotein receptor protein family at the cell surface and targets them for lysosomal degradation, which reduces the number of functional receptors. However, the adverse impact of PCSK9 on LRP1-mediated brain Aβ clearance remains elusive. By using an established BBB model, we identified reduced LRP1-mediated brain-to-blood Aβ clearance due to PCSK9 across different endothelial monolayer in vitro. Consequently, the repetitive application of FDA-approved monoclonal anti-PCSK9 antibodies into 5xFAD mice decreased the cerebral Aβ burden across variants and aggregation state, which was not reproducible in brain endothelial-specific LRP1
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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 Socratic graph.