Evidence map›Paper›PMID 42635110›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

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

Abigail J Nordbeck, Mitchell Martá-Ariza, Henric Ek Olofsson, Evgeny Kanshin, Beatrix Ueberheide, Ken Jones, Bridget Sanford, Eric D Hamlett, Elizabeth Head, Elliott J Mufson and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Abigail J NordbeckDepartment of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Mitchell Martá-ArizaCenter for Cognitive Neurology, Department of Neurology, New York University Grossman School of Medicine, New York, New York, USA.
Henric Ek OlofssonDepartment of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Evgeny KanshinProteomics Laboratory, Division of Advanced Research Technologies, New York University Grossman School of Medicine, New York, New York, USA.
Beatrix UeberheideProteomics Laboratory, Division of Advanced Research Technologies, New York University Grossman School of Medicine, New York, New York, USA.
Ken JonesDepartment of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Bridget SanfordBioinformatic Solutions LLC, Sheridan, Wyoming, USA.
Eric D HamlettDepartment of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.
Elizabeth HeadDepartment of Pathology and Laboratory Medicine, University of California Irvine, Irvine, California, USA.
Elliott J MufsonDepartment of Translational Neuroscience and Neurology, Barrow Neurological Institute, Phoenix, Arizona, USA.
Sylvia E PerezDepartment of Translational Neuroscience and Neurology, Barrow Neurological Institute, Phoenix, Arizona, USA.
Thomas WisniewskiCenter for Cognitive Neurology, Department of Neurology, New York University Grossman School of Medicine, New York, New York, USA.
Samuel GuzmanDepartment of Pathology and Neurology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Ann-Charlotte GranholmDepartment of Neurology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0002-9685-7599

Funding

TAU, AB, SYNUCLEIN AND NITRATIVE/OXIDATIVE DAMAGE IN MCIP01AG014449 · NIA · UNIVERSITY OF PITTSBURGH · PI MUFSON, ELLIOTT JAY · 1997 to 2024
$39.7M
Research Education ComponentP30AG066512 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Mary Sherman Mittelman · 2020 to 2026
$28.4M
The INCLUDE Project Down Syndrome Biorepository (DS-Biorepository)U24AG092191 · NIA · UNIVERSITY OF COLORADO DENVER · PI Joaquin M. Espinosa, Matthew D Galbraith · 2024 to 2026
$15.8M
Tau pathology in Down syndrome and Alzheimer'sRF1AG061566 · NIA · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI GRANHOLM-BENTLEY, ANN-CHARLOTTE ESTHER, MARGITTAI, MARTIN · 2019 to 2019
$3.4M
The role of immune deregulation and NGF dysmetabolism in the development of Alzheimer disease in individuals with Down syndromeR01AG087280 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI JORGE A BUSCIGLIO, A CLAUDIO CUELLO · 2024 to 2026
$3.2M
Exosome biology in Alzheimer's disease and concussion.R01AG071228 · NIA · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI GRANHOLM-BENTLEY, ANN-CHARLOTTE ESTHER, LEDREUX, AURELIE · 2021 to 2025
$3.1M
Phase I Cell Therapy for Maintaining Cholinergic Circuits in the Spectrum of Alzheimer’s DiseaseR01AG081356 · NIA · UNIVERSITY OF KENTUCKY · PI Greg A. Gerhardt, Jorge E Quintero · 2024 to 2026
$2.0M
Noradrenergic dysfunction in Down SyndromeRF1AG070153 · NIA · UNIVERSITY OF DENVER (COLORADO SEMINARY) · PI LEDREUX, AURÉLIE · 2020 to 2020
$1.8M
Default mode network dysfunction in Down SyndromeR01AG081286 · NIA · ST. JOSEPH'S HOSPITAL AND MEDICAL CENTER · PI ELLIOTT Jay MUFSON, SYLVIA EVA PEREZ · 2026 to 2026
$736k
BrightFocus Foundation CA2018010Elly Berggren FoundationLejeune Foundation GRT-2023b/2277NIA NIH HHS P01 AG014449NIA NIH HHS P30 AG066512NIA NIH HHS P30AG066512NIA NIH HHS PO1AG014449.NIA NIH HHS R01 AG071228NIA NIH HHS R01AG071228NIA NIH HHS R01 AG081286NIA NIH HHS R01 AG081356NIA NIH HHS R01AG081356-01A11NIA NIH HHS R01 AG087280NIA NIH HHS R01AG087280NIA NIH HHS RF1 AG061566NIA NIH HHS RF1 AG070153NIA NIH HHS RO1AG081286NIA NIH HHS U24 AG092191NIA NIH HHS U24AG092191-01NIH R01AG061566NIH R01AG0701531Tegger Foundation
6 · The paper itself

Abstract

introductionDown 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.

methodsWe used spatial transcriptomics and localized proteomic techniques to examine mTOR/INS signaling pathways in subregions of the hippocampus in post mortem tissue from individuals with DS-AD and age-matched neurotypical controls.

resultsmTOR pathways were significantly altered in specific hippocampal subfields in DS-AD, and INS pathways were significantly altered in dentate granule neurons. DISCUSSION: These preliminary spatial transcriptomics and localized proteomics findings demonstrate an interplay between select hippocampal mTOR/INS pathways and cellular populations, suggesting potential novel drug targets and early biomarkers for DS.

Indexed as

Alzheimer DiseaseDown SyndromeHippocampusInsulinSignal TransductionTOR Serine-Threonine KinasesFemaleHumansMaleProteomicsInsulinMTOR protein, humanTOR Serine-Threonine KinasesAlzheimer's diseaseDown syndromeinsulinlocalized proteomicsmammalian target of rapamycinpathway analysisspatial transcriptomicsupstream regulators

Identifiers

PMID42635110
PMCPMC13501503

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.