ReviewMolecular psychiatry2018
Understanding the roles of mutations in the amyloid precursor protein in Alzheimer disease.
Review in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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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.
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
53 citing papers in PubMed, 92 citations in OpenAlex.
- Aberrant phase separation from a rare ABI3 mutation drives microglial dysfunction and Alzheimer's risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A Cerebral Organoid Model of Familial Alzheimer's Disease Using Amyloid Precursor Protein Mutation, Val669Leu (International journal of stem cells · 2026Article
- Engineered APP C-terminus Alters Its Native Transcript Dynamics in Differentiated SH-SY5Y-Derived Neurons.Molecular neurobiology · 2026Article
- The difference in immunohistochemical reactivity of monoclonal antibodies against amino-terminal residues of amyloid-β peptide.Anatomical science international · 2026Article
- Alzheimer's disease PSEN-2 N141I mutation reveals altered and shear-sensitive brain endothelial cell-like phenotype in human iPSC-derived models.Acta neuropathologica communications · 2025Article
- Transient cholesterol interactions with the amyloid precursor protein involved in Alzheimer's disease pathogenesis.Biophysical reviews · 2025Review
- Key questions for the future of amyloid research in dementia: a framework for integrating complex datasets.Molecular psychiatry · 2025Review
- The pathogenic APP N-terminal Val225Ala mutation alters tau protein liquid-liquid phase separation and exacerbates synaptic damage.Molecular psychiatry · 2025Article
- The promise of gene therapy in common types of dementia.BioImpacts : BI · 2025Review
- The Icelandic Mutation (APP-A673T) Is Protective against Amyloid Pathology In Vivo.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Accumulation of neutral lipids in dystrophic neurites surrounding amyloid plaques in Alzheimer's disease.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- APP substrate ectodomain defines amyloid-β peptide length by restraining γ-secretase processivity and facilitating product release.The EMBO journal · 2023Article
- Review
- Genetics, Functions, and Clinical Impact of Presenilin-1 (PSEN1) Gene.International journal of molecular sciences · 2022Review
- Analysis of high-risk pedigrees identifies 11 candidate variants for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Prominent Effects of Berbamine Hydrochloride on Alzheimer's Disease Model Mice.Frontiers in pharmacology · 2022Article
- Knockdown of Amyloid Precursor Protein: Biological Consequences and Clinical Opportunities.Frontiers in neuroscience · 2022Review
- Plasma amyloid-β ratios in autosomal dominant Alzheimer's disease: the influence of genotype.Brain : a journal of neurology · 2021Article
- An APP ectodomain mutation outside of the Aβ domain promotes Aβ production in vitro and deposition in vivo.The Journal of experimental medicine · 2021Article
- Mutant Presenilin 1 Dysregulates Exosomal Proteome Cargo Produced by Human-Induced Pluripotent Stem Cell Neurons.ACS omega · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Many models of disease progression in Alzheimer's disease (AD) have been proposed to help guide experimental design and aid the interpretation of results. Models focussing on the genetic evidence include the amyloid cascade (ACH) and presenilin (PSH) hypotheses and the amyloid precursor protein (APP) matrix approach (AMA), of which the ACH has held a dominant position for over two decades. However, the ACH has never been fully accepted and has not yet delivered on its therapeutic promise. We review the ACH, PSH and AMA in relation to levels of APP proteolytic fragments reported from AD-associated mutations in APP. Different APP mutations have diverse effects on the levels of APP proteolytic fragments. This evidence is consistent with at least three disease pathways that can differ between familial and sporadic AD and two pathways associated with cerebral amyloid angiopathy. We cannot fully evaluate the ACH, PSH and AMA in relation to the effects of mutations in APP as the APP proteolytic system has not been investigated systematically. The confounding effects of sequence homology, complexity of competing cleavages and antibody cross reactivities all illustrate limitations in our understanding of the roles these fragments and the APP proteolytic system as a whole in normal aging and disease play. Current experimental design should be refined to generate clearer evidence, addressing both aging and complex disorders with standardised reporting formats. A more flexible theoretical framework capable of accommodating the complexity of the APP proteolytic system is required to integrate available evidence.
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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.