Evidence map›Paper›PMID 37365240›Full record

ArticleMolecular psychiatry2023

3D bioengineered neural tissue generated from patient-derived iPSCs mimics time-dependent phenotypes and transcriptional features of Alzheimer's disease.

Selene Lomoio, Ravi S Pandey, Nicolas Rouleau, Beatrice Menicacci, WonHee Kim, William L Cantley, Philip G Haydon, David A Bennett, Tracy L Young-Pearse, Gregory W Carter and 2 more

Open access · greenAbstract read
In one paragraph

Article in Molecular psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% of its field
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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Neuroinflammation in Alzheimer disease.Nature reviews. Immunology · 2025
    Review
  9. Review
  10. Review
  11. Article
  12. A framework for translating tauopathy therapeutics: Drug discovery to clinical trials.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Review
  13. Article
  14. Review
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

12 authors at 5 institutions in 2 countries.

Selene LomoioDepartment of Neuroscience, Tufts University School of Medicine, Boston, MA, USA.ORCID 0000-0002-5151-295X
Ravi S PandeyThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.ORCID 0000-0001-9567-2851
Nicolas RouleauDepartment of Health Sciences, Wilfrid Laurier University, Waterloo, Canada.
Beatrice MenicacciDepartment of Neuroscience, Tufts University School of Medicine, Boston, MA, USA.
WonHee KimDepartment of Neuroscience, Tufts University School of Medicine, Boston, MA, USA.
William L CantleyDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.ORCID 0009-0005-8270-9826
Philip G HaydonDepartment of Neuroscience, Tufts University School of Medicine, Boston, MA, USA.ORCID 0000-0001-5698-6698
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
Tracy L Young-PearseAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7846-1542
Gregory W CarterThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.ORCID 0000-0002-2834-8186
David L KaplanDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.ORCID 0000-0002-9245-7774
Giuseppina TescoDepartment of Neuroscience, Tufts University School of Medicine, Boston, MA, USA. Giuseppina.Tesco@Tufts.edu.ORCID 0000-0002-3336-7488
Tufts University · USJackson Laboratory · USBrigham and Women's Hospital · USRush University Medical Center · USWilfrid Laurier University · CA

Funding

The IU/JAX Alzheimer's Disease Precision Models Center: Rat F344U54AG054345 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI Paul Richard Territo · 2016 to 2026
$95.6M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
Rush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Pathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6M
Probing Heterogeneity of Alzheimer's Disease Using iPSCsR01AG055909 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI Tracy L YOUNG-PEARSE · 2018 to 2026
$5.7M
Study of cell-type specific Alzheimer's disease genetic variants using a novel bioengineered model of iPSC-derived neural tissueR01AG061838 · NIA · TUFTS UNIVERSITY BOSTON · PI HAYDON, PHILIP G, KAPLAN, DAVID L. · 2020 to 2024
$4.9M
A novel bioengineered model of iPSC-derived neural tissue to study of Alzheimer's diseaseR21AG065792 · NIA · TUFTS UNIVERSITY BOSTON · PI TESCO, GIUSEPPINA · 2020 to 2020
$454k
NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG055909NIA NIH HHS R01 AG061838NIA NIH HHS R21 AG065792NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NIA NIH HHS U54 AG054345
6 · The paper itself

Abstract

Several iPSC-derived three-dimensional (3D) cultures have been generated to model Alzheimer's disease (AD). While some AD-related phenotypes have been identified across these cultures, none of them could recapitulate multiple AD-related hallmarks in one model. To date, the transcriptomic features of these 3D models have not been compared with those of human AD brains. However, these data are crucial to understanding the pertinency of these models for studying AD-related pathomechanisms over time. We developed a 3D bioengineered model of iPSC-derived neural tissue that combines a porous scaffold composed of silk fibroin protein with an intercalated collagen hydrogel to support the growth of neurons and glial cells into complex and functional networks for an extended time, a fundamental requisite for aging studies. Cultures were generated from iPSC lines obtained from two subjects carrying the familial AD (FAD) APP London mutation, two well-studied control lines, and an isogenic control. Cultures were analyzed at 2 and 4.5 months. At both time points, an elevated Aβ42/40 ratio was detected in conditioned media from FAD cultures. However, extracellular Aβ42 deposition and enhanced neuronal excitability were observed in FAD culture only at 4.5 months, suggesting that extracellular Aβ deposition may trigger enhanced network activity. Remarkably, neuronal hyperexcitability has been described in AD patients early in the disease. Transcriptomic analysis revealed the deregulation of multiple gene sets in FAD samples. Such alterations were strikingly similar to those observed in human AD brains. These data provide evidence that our patient-derived FAD model develops time-dependent AD-related phenotypes and establishes a temporal relation among them. Furthermore, FAD iPSC-derived cultures recapitulate transcriptomic features of AD patients. Thus, our bioengineered neural tissue represents a unique tool to model AD in vitro over time.

Indexed as

Alzheimer DiseaseInduced Pluripotent Stem CellsNeuronsPhenotypeAmyloid beta-PeptidesAmyloid beta-Protein PrecursorBioengineeringBrainCell DifferentiationHumansNeurogliaTranscriptomeAmyloid beta-PeptidesAmyloid beta-Protein Precursor

Identifiers

PMID37365240
PMCPMC11164539
OpenAlexW4382024070

What OpenQuestion holds

Textmetadata
LicenceTDM
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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 OpenQuestion graph.