Evidence map›Paper›PMID 39077965›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024

A functional aged human iPSC-cortical neuron model recapitulates Alzheimer's disease, senescence, and the response to therapeutics.

Leandro H Gallo, Nesar Akanda, Kaveena Autar, Aakash Patel, Ian Cox, Haley A Powell, Marcella Grillo, Natali Barakat, Dave Morgan, Xiufang Guo and 1 more

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

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  8. Biosensor applications in organ-on-a-chip platforms and disease modeling.Frontiers in bioengineering and biotechnology · 2026
    Review
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  11. Article
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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

11 authors.

Leandro H GalloNanoscience Technology Center, University of Central Florida, Orlando, Florida, USA.
Nesar AkandaNanoscience Technology Center, University of Central Florida, Orlando, Florida, USA.
Kaveena AutarNanoscience Technology Center, University of Central Florida, Orlando, Florida, USA.
Aakash PatelNanoscience Technology Center, University of Central Florida, Orlando, Florida, USA.
Ian CoxNanoscience Technology Center, University of Central Florida, Orlando, Florida, USA.
Haley A PowellNanoscience Technology Center, University of Central Florida, Orlando, Florida, USA.
Marcella GrilloNanoscience Technology Center, University of Central Florida, Orlando, Florida, USA.
Natali BarakatNanoscience Technology Center, University of Central Florida, Orlando, Florida, USA.
Dave MorganDepartment of Translational Neuroscience, Michigan State University College of Human Medicine, Grand Rapids Research Center, Grand Rapids, Michigan, USA.
Xiufang GuoNanoscience Technology Center, University of Central Florida, Orlando, Florida, USA.
James J HickmanNanoscience Technology Center, University of Central Florida, Orlando, Florida, USA.

Funding

Populating MPS database with data from multi-organ, human-on-a-chip microphysiological systemsR44TR001326 · NCATS · HESPEROS, LLC · PI HICKMAN, JAMES J, SHULER, MICHAEL L · 2016 to 2021
$6.5M
Investigating the role of Alzheimer's disease familial mutations in neuromuscular physiologyR01AG077651 · NIA · UNIVERSITY OF CENTRAL FLORIDA · PI James J Hickman, David Morgan · 2022 to 2026
$3.7M
NCATS NIH HHS R44 TR001326NCATS NIH HHS R44TR001326NIA NIH HHS 5R01AG077651NIA NIH HHS R01 AG077651NIA NIH HHS R44AG05833330NIH HHS
6 · The paper itself

Abstract

introductionThe degeneration of cortical layers is associated with cognitive decline in Alzheimer's disease (AD). Current therapies for AD are not disease-modifying, and, despite substantial efforts, research and development for AD has faced formidable challenges. In addition, cellular senescence has emerged as a significant contributor to therapy resistance.

methodsHuman iPSC-derived cortical neurons were cultured on microelectrode arrays to measure long-term potentiation (LTP) noninvasively. Neurons were treated with pathogenic amyloid-β (Aβ) to analyze senescence and response to therapeutic molecules.

resultsMicrophysiological recordings revealed Aβ dampened cortical LTP activity and accelerated neuronal senescence. Aging neurons secreted inflammatory factors previously detected in brain, plasma, and cerebral spinal fluid of AD patients, in which drugs modulated senescence-related factors. DISCUSSION: This platform measures and records neuronal LTP activity in response to Aβ and therapeutic molecules in real-time. Efficacy data from similar platforms have been accepted by the FDA for neurodegenerative diseases, expediting regulatory submissions. HIGHLIGHTS: This work developed a progerontic model of amyloid-β (Aβ)-driven cortical degeneration. This work measured neuronal LTP and correlated function with aging biomarkers. Aβ is a driver of neuronal senescence and cortical degeneration. Molecules rescued neuronal function but did not halt Aβ-driven senescence. Therapeutic molecules modulated secretion of inflammatory factors by aging neurons.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesCellular SenescenceInduced Pluripotent Stem CellsNeuronsAgingCells, CulturedCerebral CortexHumansLong-Term PotentiationAmyloid beta-PeptidesagingAlzheimer's diseaseamyloidelectrophysiologyinflammationmicroelectrodesneurodegenerationsenescencetautherapeutics

Identifiers

PMID39077965
PMCPMC11633364

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.