Evidence map›Paper›PMID 41988945›Full record

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

Evaluating the peripheral nervous system pathology of Alzheimer's disease utilizing a functional human NMJ microphysiological system.

Akhmetzada Kargazhanov, Romy Aiken, Kenneth Hawkins, Rafael Lopez, Ahmad Nawaz, Gaurav Srivastava, Chase Miller, Will Bogen, Christopher Long, David Morgan and 2 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. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. A peripheral perspective on brain health: vascular and skeletal muscle contributions.American journal of physiology. Heart and circulatory physiology · 2026
    Review
  2. Article
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.

Akhmetzada KargazhanovHybrid Systems Lab, NanoScience Technology Center, University of Central Florida, Orlando, Florida, USA.
Romy AikenHybrid Systems Lab, NanoScience Technology Center, University of Central Florida, Orlando, Florida, USA.
Kenneth HawkinsHybrid Systems Lab, NanoScience Technology Center, University of Central Florida, Orlando, Florida, USA.
Rafael LopezHybrid Systems Lab, NanoScience Technology Center, University of Central Florida, Orlando, Florida, USA.
Ahmad NawazHybrid Systems Lab, NanoScience Technology Center, University of Central Florida, Orlando, Florida, USA.
Gaurav SrivastavaHybrid Systems Lab, NanoScience Technology Center, University of Central Florida, Orlando, Florida, USA.
Chase MillerHesperos Inc., Orlando, Florida, USA.
Will BogenHesperos Inc., Orlando, Florida, USA.
Christopher LongHesperos Inc., Orlando, Florida, USA.
David MorganDepartment of Translational Neuroscience, Michigan State University College of Human Medicine, Grand Rapids, Michigan, USA.
Xiufang GuoHybrid Systems Lab, NanoScience Technology Center, University of Central Florida, Orlando, Florida, USA.
James HickmanHybrid Systems Lab, NanoScience Technology Center, University of Central Florida, Orlando, Florida, USA.

Funding

Modulatory Role of Blood-Brain-Barrier and Enzymatic Activity in an Innovative Human Model of Cholinergic Drug Induced DementiaR44AG071386 · NIA · HESPEROS, LLC · PI James J Hickman, Jacques Turgeon · 2021 to 2026
$5.0M
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
Institute of Aging at National Institutes of Health R01AG077651Institute of Aging at National Institutes of Health R44AG071386NIA NIH HHS R01 AG077651NIA NIH HHS R44 AG071386
6 · The paper itself

Abstract

introductionAlzheimer's Disease (AD) is a central nervous system (CNS) neurodegenerative disease leading to dementia, but can also show symptoms of motor deficits. It is not clear whether the peripheral motor deficits in AD are derived from upstream centers or intrinsic to the neuromuscular circuit. This study developed a model to evaluate the neuromuscular pathology of familial AD (fAD) in a functional neuromuscular junction (NMJ) system.

methodsThe fAD iPSC motoneurons (MNs), together with healthy iPSC skeletal myoblasts (SKM), were adapted into a dual chamber NMJ system. The formation and function of the NMJs formed were evaluated utilizing clinically translatable readouts.

resultsFunctional analysis indicated that NMJs formed with fAD MNs showed severe (PSEN1 A246E) to moderate (APP K595N/M596L) deficiencies in NMJ function. DISCUSSION: These findings confirmed that fAD mutations lead to NMJ deficiencies, supporting that motor deficits can be induced independently from cognitive deficits.

Indexed as

Alzheimer DiseaseMotor NeuronsNeuromuscular JunctionAmyloid beta-Protein PrecursorHumansInduced Pluripotent Stem CellsMicrophysiological SystemsMyoblastsPresenilin-1Amyloid beta-Protein PrecursorPresenilin-1fAD NMJ pathologyfamilial Alzheimer's diseasemicrophysilogical systemmotoneuronsneuromuscular junctionperipheral nervous system

Identifiers

PMID41988945
PMCPMC13084706

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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.