ArticleMolecular pharmaceutics2012
Differences in the cellular uptake and intracellular itineraries of amyloid beta proteins 40 and 42: ramifications for the Alzheimer's drug discovery.
Article in Molecular pharmaceutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
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Who cites it
35 citing papers in PubMed, 63 citations in OpenAlex.
- UPS-mediated P-glycoprotein regulation in Alzheimer's disease: pharmacological implications for the amyloid pathology.Molecular biology reports · 2026Review
- Therapeutic Options for Alzheimer's Disease and Aging-Associated Cognitive Decline: State of the Art in the ACH2.0 Paradigm.International journal of molecular sciences · 2026Review
- Brain insulin resistance mediated cognitive impairment and neurodegeneration: Type-3 diabetes or Alzheimer's Disease.Acta neurologica Belgica · 2025Review
- Alzheimer's Is a Multiform Disease of Sustained Neuronal Integrated Stress Response Driven by the C99 Fragment Generated Independently of AβPP; Proteolytic Production of Aβ Is Suppressed in AD-Affected Neurons: Evolution of a Theory.International journal of molecular sciences · 2025Review
- Article
- Quintessential Synergy: Concurrent Transient Administration of Integrated Stress Response Inhibitors and BACE1 and/or BACE2 Activators as the Optimal Therapeutic Strategy for Alzheimer's Disease.International journal of molecular sciences · 2024Article
- ACH2.0/E, the Consolidated Theory of Conventional and Unconventional Alzheimer's Disease: Origins, Progression, and Therapeutic Strategies.International journal of molecular sciences · 2024Review
- On the Inadequacy of the Current Transgenic Animal Models of Alzheimer's Disease: The Path Forward.International journal of molecular sciences · 2024Article
- Clathrin mediated endocytosis in Alzheimer's disease: cell type specific involvement in amyloid beta pathology.Frontiers in aging neuroscience · 2024Review
- Next Generation Therapeutic Strategy for Treatment and Prevention of Alzheimer's Disease and Aging-Associated Cognitive Decline: Transient, Once-in-a-Lifetime-Only Depletion of Intraneuronal Aβ (International journal of molecular sciences · 2023Article
- Amyloid-Beta Peptides 40 and 42 Employ Distinct Molecular Pathways for Cell Entry and Intracellular Transit at the Blood-Brain Barrier Endothelium.Molecular pharmacology · 2023Article
- The Amyloid Cascade Hypothesis 2.0 for Alzheimer's Disease and Aging-Associated Cognitive Decline: From Molecular Basis to Effective Therapy.International journal of molecular sciences · 2023Article
- The Amyloid Cascade Hypothesis 2.0: Generalization of the Concept.Journal of Alzheimer's disease reports · 2023Article
- Principles of Design of Clinical Trials for Prevention and Treatment of Alzheimer's Disease and Aging-Associated Cognitive Decline in the ACH2.0 Perspective: Potential Outcomes, Challenges, and Solutions.Journal of Alzheimer's disease reports · 2023Article
- Effect of Lecanemab in Early Alzheimer's Disease: Mechanistic Interpretation in the Amyloid Cascade Hypothesis 2.0 Perspective.Journal of Alzheimer's disease : JAD · 2023Article
- AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice.Traffic (Copenhagen, Denmark) · 2023Article
- Amentoflavone Promotes Cellular Uptake and Degradation of Amyloid-Beta in Neuronal Cells.International journal of molecular sciences · 2022Article
- Article
- Circadian control of heparan sulfate levels times phagocytosis of amyloid beta aggregates.PLoS genetics · 2022Article
- The Amyloid Cascade Hypothesis 2.0: On the Possibility of Once-in-a-Lifetime-Only Treatment for Prevention of Alzheimer's Disease and for Its Potential Cure at Symptomatic Stages.Journal of Alzheimer's disease reports · 2022Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
Abstract
Mounting evidence suggests that the pathological hallmarks of Alzheimer's disease (AD), neurofibrillary tangles and parenchymal amyloid plaques, are downstream reflections of neurodegeneration caused by the intraneuronal accumulation of amyloid-β proteins (Aβ), particularly Aβ42 and Aβ40. While the neurotoxicity of more amyloidogenic but less abundant Aβ42 is well documented, the effect of Aβ40 on neurons has been understudied. The Aβ40 expression in the presymptomatic AD brain is ten times greater than that of Aβ42. However, the Aβ40:42 ratio decreases with AD progression and coincides with increased amyloid plaque deposition in the brain. Hence, it is thought that Aβ40 protects neurons from the deleterious effects of Aβ42. The pathophysiological pathways involved in the neuronal uptake of Aβ40 or Aβ42 have not been clearly elucidated. Lack of such critical information obscures therapeutic targets and thwarts rational drug development strategies aimed at preventing neurodegeneration in AD. The current study has shown that fluorescein labeled Aβ42 (F-Aβ42) is internalized by neurons via dynamin dependent endocytosis and is sensitive to membrane cholesterol, whereas the neuronal uptake of F-Aβ40 is energy independent and nonendocytotic. Following their uptake, both F-Aβ40 and F-Aβ42 did not accumulate in early/recycling endosomes; F-Aβ42 but not F-Aβ40 accumulated in late endosomes and in the vesicles harboring caveolin-1. Furthermore, F-Aβ42 demonstrated robust accumulation in the lysosomes and damaged their integrity, whereas F-Aβ40 showed only a sparse lysosomal accumulation. Such regulated trafficking along distinct pathways suggests that Aβ40 and Aβ42 exercise differential effects on neurons. These differences must be carefully considered in the design of a pharmacological agent intended to block the neurodegeneration triggered by Aβ proteins.
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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.