ArticleAging cell2025
Elevated p16Ink4a Expression Enhances Tau Phosphorylation in Neurons Differentiated From Human-Induced Pluripotent Stem Cells.
Article in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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
2 citing papers in PubMed.
- Cell Cycle Dysfunction and Metabolic Alterations Consistent With Pathological Tau in Progressive Supranuclear Palsy Derived Fibroblasts.Molecular neurobiology · 2026Article
- Introducing Cellular Senescence in Human Induced Pluripotent Stem Cells and Differentiated Neural Lineage for Modeling of Age-Associated Diseases.Advanced biology · 2026Article
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
Increased expression of the cyclin-dependent kinase inhibitor p16Ink4a (p16) is detected in neurons of human Alzheimer's disease (AD) brains and during normal aging. Importantly, selective eliminating p16-expressing cells in AD mouse models attenuates tau pathologies and improves cognition. But whether and how p16 contributes to AD pathogenesis remains unclear. To address this question, we tested whether induction of p16 expression in neurons exacerbates AD pathologies. We created a doxycycline-inducible system to trigger p16 up-regulation in human-induced pluripotent stem cells (iPSCs) and neurons differentiated from iPSCs. We demonstrated that up-regulated p16 expression in iPSCs reduces cell proliferation, down-regulates cell cycle genes, and up-regulates genes involved in focal adhesion, interferon α response and PI3K-Akt signaling. Our approach enables temporal control of p16 induction upon differentiation from iPSCs to neurons. In differentiated cortical neurons, we found that up-regulation of p16 increases tau phosphorylation at Ser202/Thr205 and Thr231 in a cell-autonomous manner, while amyloid beta secretion is not affected. These data suggest a critical role of p16 in regulating tau phosphorylation in neurons, and thereby contributing to pathological progression of AD. As pathological tau tangles have been shown to induce p16 expression, our studies suggest a positive feedback loop between p16 and tau to exacerbate tau pathologies.
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.