Oliver's mTOR Atlas Evidence Platform
Reading level
Mode

Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations

Nordbeck AJ, Martá-Ariza M, Ek Olofsson H, Kanshin E, Ueberheide B et al. · 2026 · Alzheimer's & Dementia · Atlas ID NOR2026

What this study shows

Spatial transcriptomics plus localized proteomics on human post-mortem hippocampus show that mTOR pathway signalling is significantly altered in specific hippocampal subfields in Down syndrome with Alzheimer's disease neuropathology, while insulin pathway signalling is altered specifically in dentate granule neurons — pointing to subregion- and cell-type-specific mTOR/insulin dysregulation rather than a uniform whole-tissue shift. Explicitly framed by the authors as preliminary.

Abstract

ShowHide

Down syndrome (DS) is caused by a complete or partial trisomy of chromosome 21, resulting in variable intellectual disabilities and a high risk for early-onset Alzheimer's disease (DS-AD). Dysregulation of the mammalian target of rapamycin (mTOR) and insulin (INS) signaling pathways has been reported in DS. We hypothesized that upstream alterations in these two pathways contribute to hippocampal dysfunction in DS-AD.

Read the full abstract on PubMed →

At a glance

Evidence type M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human post-mortem hippocampus (Down syndrome with AD neuropathology vs neurotypical controls)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type5 - Mechanistic / In Vitro
Model systemHuman post-mortem hippocampus (Down syndrome with AD neuropathology vs neurotypical controls)
JournalAlzheimer's & Dementia
Year2026
Peer reviewedYes
Record last updated2026-08-22
SourceDOI 10.1002/alz.71776 · PMID 42635110 · Free full text (PMC13501503)

Cite this paper

ShowHide 
Nordbeck, A. J., et al. (2026). Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations. Alzheimer's & Dementia. https://doi.org/10.1002/alz.71776

@article{NOR2026,
  author       = {Nordbeck, A. J. and Martá-Ariza, M. and Ek Olofsson, H. and Kanshin, E. and Ueberheide, B. and others},
  title        = {{Disruption of hippocampal upstream regulators of mTOR and insulin pathways in Down syndrome with Alzheimer's disease neuropathology: Preliminary observations}},
  journal      = {Alzheimer's & Dementia},
  year         = {2026},
  doi          = {10.1002/alz.71776},
  note         = {PMID: 42635110},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper. 

Barton, O. (2026). Oliver's mTOR Atlas (record NOR2026) [Data set]. https://mtor-atlas.org/study/NOR2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_NOR2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record NOR2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/NOR2026/},
  doi          = {10.5281/zenodo.22059963}
}