ArticleTranslational psychiatry2020
Alzheimer's disease-related dysregulation of mRNA translation causes key pathological features with ageing.
Article in Translational psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- The Caribbean-Hispanic Alzheimer's disease brain transcriptome reveals ancestry-specific disease mechanisms.Neurobiology of disease · 2023Pooled it
- Distinct single-nucleus RNA-seq changes among non-neuronal cells in ADNC, LATE-NC, and mixed pathologies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- SIEVEseq: unified differential expression, variability, and skewness analyses using RNA-Seq data.DNA research : an international journal for rapid publication of reports on genes and genomes · 2026Article
- Endogenously generated Dutch-type Aβ non-fibrillar aggregates dysregulate presynaptic neurotransmission in the absence of detectable inflammation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Low concentrations of amyloid-beta oligomers induce synaptogenesis characteristic for mild cognitive impairment and alter the de novo proteome.Translational psychiatry · 2026Article
- Time-resolved phenotyping of seizure evolution in developmental and epileptic encephalopathy: insights and gaps from the CYFIP2 Arg87Cys mouse model.Frontiers in synaptic neuroscience · 2026Review
- Unraveling the molecular mechanisms in severe Alzheimer's disease based on transcriptomic data using next generation knowledge discovery methods.Pakistan journal of medical sciences · 2026Article
- Mutant Tau (P301L) Enhances Global Protein Translation in Differentiated SH-SY5Y Cells by Upregulating mTOR Signalling.International journal of molecular sciences · 2026Article
- Dysregulated mRNA Translation in Alzheimer's Disease: Mechanisms, Therapeutic Opportunities, and Challenges for Clinical Translation.Clinical interventions in aging · 2026Review
- RNA Granules at the Crossroads of Synaptic Dysfunction and Neurodegeneration.Journal of neurochemistry · 2025Review
- Extracellular Vesicles-Dependent Secretion Regulates Intracellular CYFIP2 Protein Homeostasis in Cortical Neurons.Biomedicines · 2025Article
- Species-specific sensitivity to intracerebroventricular streptozotocin in rats and mice highlights pathways and proteins relevant to Alzheimer's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Plasma proteomic analysis identifies proteins and pathways related to Alzheimer's risk.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Deficits of Alzheimer's Disease Neuropsychological Architecture Correlate with Specific Exosomal mRNA Expression: Evidence of a Continuum?International journal of molecular sciences · 2025Article
- Spatial and Temporal Single-Cell Profiling of RNA Compartmentalization in Neurons with Nanotweezers.ACS nano · 2025Article
- Seeding-competent early tau multimers are associated with cell type-specific transcriptional signatures.Acta neuropathologica · 2025Article
- The WAVE complex in developmental and adulthood brain disorders.Experimental & molecular medicine · 2025Review
- Cold-raising unmasks sleep disruption in amicroPublication biology · 2025Article
- Organelle abnormalities in Alzheimer's disease.Organelle (Tucson, Ariz.) · 2025Article
- Quantitative Imaging of Regional Cerebral Protein Synthesis in Clinical Alzheimer's Disease by [Molecular imaging and biology · 2024Article
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 at 1 institution in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is characterised by Aβ and tau pathology as well as synaptic degeneration, which correlates best with cognitive impairment. Previous work suggested that this pathological complexity may result from changes in mRNA translation. Here, we studied whether mRNA translation and its underlying signalling are altered in an early model of AD, and whether modelling this deficiency in mice causes pathological features with ageing. Using an unbiased screen, we show that exposure of primary neurons to nanomolar amounts of Aβ increases FMRP-regulated protein synthesis. This selective regulation of mRNA translation is dependent on a signalling cascade involving MAPK-interacting kinase 1 (Mnk1) and the eukaryotic initiation factor 4E (eIF4E), and ultimately results in reduction of CYFIP2, an FMRP-binding protein. Modelling this CYFIP2 reduction in mice, we find age-dependent Aβ accumulation in the thalamus, development of tau pathology in entorhinal cortex and hippocampus, as well as gliosis and synapse loss in the hippocampus, together with deficits in memory formation. Therefore, we conclude that early stages of AD involve increased translation of specific CYFIP2/FMRP-regulated transcripts. Since reducing endogenous CYFIP2 expression is sufficient to cause key features of AD with ageing in mice, we suggest that prolonged activation of this pathway is a primary step toward AD pathology, highlighting a novel direction for therapeutic targeting.
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.