Evidence map›Paper›PMID 37924159›Full record

ArticleMolecular brain2023

Limitations of the human iPSC-derived neuron model for early-onset Alzheimer's disease.

Phoebe Valdes, Kenneth W Henry, Michael Q Fitzgerald, Koushik Muralidharan, Andrew B Caldwell, Srinivasan Ramachandran, Lawrence S B Goldstein, William C Mobley, Douglas R Galasko, Shankar Subramaniam

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular brain, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 32% 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

4 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. 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

10 authors at 2 institutions in 1 country.

Phoebe ValdesDepartment of Bioengineering, University of California, La Jolla, San Diego, CA, USA.ORCID 0000-0003-3165-7235
Kenneth W HenryDepartment of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, CA, USA.ORCID 0009-0004-3440-107X
Michael Q FitzgeraldDepartment of Bioengineering, University of California, La Jolla, San Diego, CA, USA.ORCID 0000-0002-3693-0854
Koushik MuralidharanMedical Scientist Training Program, University of California, La Jolla, San Diego, CA, USA.ORCID 0000-0001-5651-5335
Andrew B CaldwellDepartment of Bioengineering, University of California, La Jolla, San Diego, CA, USA.ORCID 0000-0002-2850-7677
Srinivasan RamachandranDepartment of Bioengineering, University of California, La Jolla, San Diego, CA, USA.ORCID 0000-0002-4912-0279
Lawrence S B GoldsteinDepartment of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, CA, USA.ORCID 0000-0003-0636-9186
William C MobleyDepartment of Neurosciences, University of California, La Jolla, San Diego, CA, USA.ORCID 0000-0002-6408-9548
Douglas R GalaskoDepartment of Neurosciences, University of California, La Jolla, San Diego, CA, USA.ORCID 0000-0001-6195-3241
Shankar SubramaniamDepartment of Bioengineering, University of California, La Jolla, San Diego, CA, USA. shankar@ucsd.edu.ORCID 0000-0002-8059-4659
University of California San Diego · USLa Jolla Bioengineering Institute · US

Funding

UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DOUGLAS R GALASKO · 2019 to 2026
$34.9M
Reconstruction and Modeling of Dynamical Molecular NetworksR01LM012595 · NLM · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SUBRAMANIAM, SHANKAR · 2018 to 2021
$1.3M
Illumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600k
NIA NIH HHS P30 AG062429NIH HHS R01-LM012595NIH HHS S10 OD026929NLM NIH HHS R01 LM012595
6 · The paper itself

Abstract

Non-familial Alzheimer's disease (AD) occurring before 65 years of age is commonly referred to as early-onset Alzheimer's disease (EOAD) and constitutes ~ 5-6% of all AD cases (Mendez et al. in Continuum 25:34-51, 2019). While EOAD exhibits the same clinicopathological changes such as amyloid plaques, neurofibrillary tangles (NFTs), brain atrophy, and cognitive decline (Sirkis et al. in Mol Psychiatry 27:2674-88, 2022; Caldwell et al. in Mol Brain 15:83, 2022) as observed in the more prevalent late-onset AD (LOAD), EOAD patients tend to have more severe cognitive deficits, including visuospatial, language, and executive dysfunction (Sirkis et al. in Mol Psychiatry 27:2674-88, 2022). Patient-derived induced pluripotent stem cells (iPSCs) have been used to model and study penetrative, familial AD (FAD) mutations in APP, PSEN1, and PSEN2 (Valdes et al. in Research Square 1-30, 2022; Caldwell et al. in Sci Adv 6:1-16, 2020) but have been seldom used for sporadic forms of AD that display more heterogeneous disease mechanisms. In this study, we sought to characterize iPSC-derived neurons from EOAD patients via RNA sequencing. A modest difference in expression profiles between EOAD patients and non-demented control (NDC) subjects resulted in a limited number of differentially expressed genes (DEGs). Based on this analysis, we provide evidence that iPSC-derived neuron model systems, likely due to the loss of EOAD-associated epigenetic signatures arising from iPSC reprogramming, may not be ideal models for studying sporadic AD.

Indexed as

Alzheimer DiseaseInduced Pluripotent Stem CellsHumansMutationNeuronsEarly-onset Alzheimer’s diseaseiPSC neuronsRNA-seqSystems biology

Identifiers

PMID37924159
PMCPMC10623777
OpenAlexW4388293797

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.