ArticleScience (New York, N.Y.)2012
The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol.
Article in Science (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 261 papers, 1 of them a synthesis 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
261 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cholesterol, 24-Hydroxycholesterol, and 27-Hydroxycholesterol as Surrogate Biomarkers in Cerebrospinal Fluid in Mild Cognitive Impairment and Alzheimer's Disease: A Meta-Analysis.Journal of Alzheimer's disease : JAD · 2016Pooled it
- CYP46A1 activation by low-dose efavirenz enhances brain cholesterol metabolism in subjects with early Alzheimer's disease.Alzheimer's research & therapy · 2022Trial
- Cardiolipin Modulates the Activity of the Intramembrane Protease GlpG Inducing Membrane Restructuring.Journal of the American Chemical Society · 2026Article
- Accurate determination of the preferred aggregation number of a micelle-encapsulated membrane protein dimer.Biophysical journal · 2026Article
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Valosin-containing protein is cargo in Amyloid Precursor Protein extracellular vesicles.Cell communication and signaling : CCS · 2026Article
- Advances in EPR Approaches for Studying Structural Properties of Membrane Proteins.Magnetic resonance in chemistry : MRC · 2026Review
- Conformational Flexibility of Transmembrane Helices: How it Works and Where it Matters.Chemical reviews · 2026Review
- Article
- Veraguamide E, a Marine Cyanobacterial Depsipeptide Targeting σJournal of natural products · 2025Article
- Accurate determination of the preferred aggregation number of a micelle-encapsulated membrane protein dimer.bioRxiv : the preprint server for biology · 2025Article
- Structural Dynamics and Topology of Human KCNE3 in Lipid Bilayers Studied by Site-Directed Spin Labeling and Electron Paramagnetic Resonance Spectroscopy.The journal of physical chemistry. B · 2025Article
- Transient cholesterol interactions with the amyloid precursor protein involved in Alzheimer's disease pathogenesis.Biophysical reviews · 2025Review
- ApoE4 requires lipidation enhancement to resolve cellular lipid and protein abnormalities following NPC1 inhibition.Scientific reports · 2025Article
- Diverse Interactions of Sterols with Amyloid Precursor Protein Transmembrane Domain Can Shift Distribution Between Alternative Amyloid-β Production Cascades in Manner Dependent on Local Lipid Environment.International journal of molecular sciences · 2025Article
- Aggregation Behavior of Amyloid Beta Peptide Depends Upon the Membrane Lipid Composition.The Journal of membrane biology · 2024Review
- Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease.Annual review of biophysics · 2024Review
- Nanodisc Reconstitution and Characterization of Amyloid-β Precursor Protein C99.Analytical chemistry · 2024Article
- Optimizing NMR fragment-based drug screening for membrane protein targets.Journal of structural biology: X · 2024Article
- The Intersection of cerebral cholesterol metabolism and Alzheimer's disease: Mechanisms and therapeutic prospects.Heliyon · 2024Review
201 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.
Funding
Abstract
C99 is the transmembrane carboxyl-terminal domain of the amyloid precursor protein that is cleaved by γ-secretase to release the amyloid-β polypeptides, which are associated with Alzheimer's disease. Nuclear magnetic resonance and electron paramagnetic resonance spectroscopy show that the extracellular amino terminus of C99 includes a surface-embedded "N-helix" followed by a short "N-loop" connecting to the transmembrane domain (TMD). The TMD is a flexibly curved α helix, making it well suited for processive cleavage by γ-secretase. Titration of C99 reveals a binding site for cholesterol, providing mechanistic insight into how cholesterol promotes amyloidogenesis. Membrane-buried GXXXG motifs (G, Gly; X, any amino acid), which have an established role in oligomerization, were also shown to play a key role in cholesterol binding. The structure and cholesterol binding properties of C99 may aid in the design of Alzheimer's therapeutics.
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What Socratic 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 Socratic graph.