ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Calpain Activation in Alzheimer's Model Mice Is an Artifact of APP and Presenilin Overexpression.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 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
71 citing papers in PubMed, 117 citations in OpenAlex.
- Unique transcriptomic alterations in 5XFAD;PS19 mouse model identify glial lipid dysregulation and coordinated microglial-oligodendrocyte responses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Early glymphatic failure in AppNL-F knock-in mice is linked to parenchymal border macrophages loss.Brain : a journal of neurology · 2026Article
- Amyloid exacerbates tau and alpha-synuclein pathologies, behavioral impairments, and neuroinflammation in a mixed dementia model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Considerations for the selection and phenotyping of mouse models for the study of Alzheimer's disease.STAR protocols · 2026Review
- Valosin-containing protein is cargo in Amyloid Precursor Protein extracellular vesicles.Cell communication and signaling : CCS · 2026Article
- Effects of West Nile Virus on behavioral and cognitive performance, circadian body temperatures, cortical Aβ and p-tau pathology, and immune measures in human apoE and human amyloid precursor protein NL-G-F/human apoE mice.Frontiers in immunology · 2026Article
- Epigenetic and transcriptomic alterations precede amyloidosis in the Alzheimer's disease AppScientific reports · 2025Article
- Amyloid Beta in Alzheimer's Disease: Mechanisms, Biomarker Potential, and Therapeutic Targets.CNS neuroscience & therapeutics · 2025Review
- Sex-Dependent Changes in the Gene Expression of UPR-Associated Calcium-Binding Proteins in the STZ-Induced Model of Alzheimer's Disease.Molecular neurobiology · 2025Article
- Article
- Reactive Astrocytes with Reduced Function of Glutamate Transporters in theACS chemical neuroscience · 2025Article
- Human MAPT knockin mouse models of frontotemporal dementia for the neurodegenerative research community.Cell reports methods · 2025Article
- Effects of West Nile virus on behavioral and cognitive performance, cortical Aβ pathology, viral loads, and immune measures of middle-aged NL-G-F/E3 and NL-G-F/E4 mice.Frontiers in aging neuroscience · 2025Article
- Hippocampal Synaptic Plasticity: Integrating Memory and Anxiety Impairments in the Early Stages of Alzheimer's Disease.Current topics in behavioral neurosciences · 2025Review
- Lost in translation: Inconvenient truths on the utility of mouse models in Alzheimer's disease research.eLife · 2024Review
- Article
- Hippocampal injections of soluble amyloid-beta oligomers alter electroencephalographic activity during wake and slow-wave sleep in rats.Alzheimer's research & therapy · 2023Article
- Cognitive decline in diabetic mice predisposed to Alzheimer's disease is greater than in wild type.Life science alliance · 2023Article
- Selective dysfunction of fast-spiking inhibitory interneurons and disruption of perineuronal nets in a tauopathy mouse model.iScience · 2023Article
- From synapses to circuits and back: Bridging levels of understanding in animal models of Alzheimer's disease.The European journal of neuroscience · 2022Review
11 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
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledIntraneuronal calcium stimulates the calpain-dependent conversion of p35 to p25, a CDK5 activator. It is widely believed that amyloid β peptide (Aβ) induces this conversion that, in turn, has an essential role in Alzheimer's disease pathogenesis. However, in vivo studies on p25 generation used transgenic mice overexpressing mutant amyloid precursor protein (APP) and presenilin (PS). Here, using single App knock-in mice, we show that p25 generation is an artifact caused by membrane protein overexpression. We show that massive Aβ42 accumulation without overexpression of APP or presenilin does not produce p25, whereas p25 generation occurred with APP/PS overexpression and in postmortem mouse brain. We further support this finding using mice deficient for calpastatin, the sole calpain-specific inhibitor protein. Thus, the intracerebral environment of the APP/PS mouse brain and postmortem brain is an unphysiological state. SIGNIFICANCE STATEMENT: We recently estimated using single App knock-in mice that accumulate amyloid β peptide without transgene overexpression that 60% of the phenotypes observed in Alzheimer's model mice overexpressing mutant amyloid precursor protein (APP) or APP and presenilin are artifacts (Saito et al., 2014). The current study further supports this estimate by invalidating key results from papers that were published in Cell These findings suggest that more than 3000 publications based on APP and APP/PS overexpression must be reevaluated.
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.