ReviewProtein science : a publication of the Protein Society2019
The vexing complexity of the amyloidogenic pathway.
Review in Protein science : a publication of the Protein Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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
21 citing papers in PubMed, 34 citations in OpenAlex.
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Navigating the treatment landscape of Alzheimer's disease: Current strategies and future directions.Ibrain · 2025Review
- Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease.Annual review of biophysics · 2024Review
- Optimizing NMR fragment-based drug screening for membrane protein targets.Journal of structural biology: X · 2024Article
- A novel mouse model for N-terminal truncated Aβ2-x generation through meprin β overexpression in astrocytes.Cellular and molecular life sciences : CMLS · 2024Article
- Co-treatment with the seed ofFood science & nutrition · 2024Article
- Lipid Peroxidation Drives Liquid-Liquid Phase Separation and Disrupts Raft Protein Partitioning in Biological Membranes.Journal of the American Chemical Society · 2024Article
- The Roles of the Amyloid Beta Monomers in Physiological and Pathological Conditions.Biomedicines · 2023Review
- The Binding of Different Substrate Molecules at the Docking Site and the Active Site of γ-Secretase Can Trigger Toxic Events in Sporadic and Familial Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Contribution of hyperglycemia-induced changes in microglia to Alzheimer's disease pathology.Pharmacological reports : PR · 2022Review
- Article
- Amyloid Beta Dynamics in Biological Fluids-Therapeutic Impact.Journal of clinical medicine · 2021Review
- The transmembrane amyloid precursor C99 protein exhibits non-specific interaction with tau.Biochemical and biophysical research communications · 2021Article
- Inhibition of Astrocytic HistamineBiomolecules · 2021Review
- Targeting γ-Secretase for Familial Alzheimer's Disease.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2021Article
- Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer's Disease.Biomedicines · 2020Review
- Impact of Cholesterol Concentration and Lipid Phase on Structure and Fluctuation of Amyloid Precursor Protein.The journal of physical chemistry. B · 2020Article
- Genetic intolerance analysis as a tool for protein science.Biochimica et biophysica acta. Biomembranes · 2020Review
- Mosaic Somatic Gene Recombination as a Potentially Unifying Hypothesis for Alzheimer's Disease.Frontiers in genetics · 2020Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The role of the amyloidogenic pathway in the etiology of Alzheimer's disease (AD), particularly the common sporadic late onset forms of the disease, is controversial. To some degree, this is a consequence of the failure of drug and therapeutic antibody trials based either on targeting the proteases in this pathway or its amyloid end products. Here, we explore the formidable complexity of the biochemistry and cell biology associated with this pathway. For example, we review evidence that the immediate precursor of amyloid-β, the C99 domain of the amyloid precursor protein (APP), may itself be toxic. We also review important new results that appear to finally establish a direct genetic link between mutations in APP and the sporadic forms of AD. Based on the complexity of amyloidogenesis, it seems possible that a major contributor to the failure of related drug trials is that we have an incomplete understanding of this pathway and how it is linked to Alzheimer's pathogenesis. If so, this highlights a need for further characterization of this pathway, not its abandonment.
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.