Evidence map›Paper›PMID 41776543›Full record

ArticleMolecular brain2026

Recapitulating Alzheimer's disease pathophysiology with a microfluidic neurospheroid-grafted endothelial barrier model.

Samuel Chidiebere Uzoechi, Charity Johnson-Campbell, Cody Joseph Badeaux, Sang Su Kwak, Doo Yeon Kim, Yeoheung Yun

Abstract read
In one paragraph

Article in Molecular brain, 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
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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

6 authors.

Samuel Chidiebere UzoechiFIT BEST Laboratory, Department of Chemical, Biological and Bio Engineering, NERVE Center, North Carolina Agricultural and Technical State University, Greensboro, NC, 27411, USA.
Charity Johnson-CampbellFIT BEST Laboratory, Department of Chemical, Biological and Bio Engineering, NERVE Center, North Carolina Agricultural and Technical State University, Greensboro, NC, 27411, USA.
Cody Joseph BadeauxFIT BEST Laboratory, Department of Chemical, Biological and Bio Engineering, NERVE Center, North Carolina Agricultural and Technical State University, Greensboro, NC, 27411, USA.
Sang Su KwakGenetics and Aging Research Unit, Mass General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Doo Yeon KimGenetics and Aging Research Unit, Mass General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Yeoheung YunFIT BEST Laboratory, Department of Chemical, Biological and Bio Engineering, NERVE Center, North Carolina Agricultural and Technical State University, Greensboro, NC, 27411, USA. yyun@ncat.edu.

Funding

Alzheimer's disease-replicated brain microphysiological system to model AD physiopathology and its influenceon gliovasculature and immune systemSC1NS122448 · NINDS · NORTH CAROLINA AGRI & TECH ST UNIV · PI YUN, YEOHEUNG · 2021 to 2024
$1.4M
Center for Neurovascular Engineering Research and adVanced Education (NERVE)UG3EB036466 · NIBIB · NORTH CAROLINA AGRI & TECH ST UNIV · PI Yeoheung Yun · 2024 to 2026
$1.2M
Cure Alzheimer's Fund A069137National Science Foundation 2429044NIBIB NIH HHS UG3 EB036466NIH HHS 1R01AG082093-01NIH HHS 1UG3EB036466-01NINDS NIH HHS SC1 NS122448
6 · The paper itself

Abstract

backgroundTraditional two-dimensional (2D) models do not adequately capture the complex cellular interactions, brain-specific architecture, and progressive pathology of Alzheimer's disease (AD). Three-dimensional (3D) organoid and microfluidic technologies provide more physiologically relevant platforms for studying AD-associated neurovascular dysfunction.

methodsWe developed a membrane-free microfluidic endothelial barrier model integrated with neurospheroids derived from familial AD (FAD) neural progenitor cells. Human endothelial cells were cultured within perfusable microfluidic channels to establish a vascular-like interface rather than a fully specialized BBB endothelium. Pre-differentiated neurospheroids were grafted into the brain chamber. Endothelial barrier integrity, tight-junction expression, phosphorylated tau (pTau), and Aβ42/Aβ40 production and distribution between compartments were assessed using immunofluorescence imaging and ELISA.

resultsThe neurospheroid-grafted endothelial barrier construct captured key AD-associated phenotypes. ReN-AD-D4 models exhibited increased endothelial barrier permeability, reduced ZO-1 expression, and elevated pTau relative to controls. The platform supported endogenous Aβ generation, accumulation, and endothelial-associated deposition at the endothelial barrier. ELISA demonstrated differential Aβ42 and Aβ40 distribution, consistent with isoform-selective behavior reported in AD pathology. Collectively, these results indicate co-occurring neuronal and endothelial barrier alterations within the integrated 3D system.

conclusionThis microfluidic endothelial barrier-neurospheroid platform enables quantitative assessment of amyloid-β accumulation, spatial distribution, and compartmentalized secretion alongside tau pathology and endothelial barrier integrity changes. Integrating human endothelial monolayers with FAD-derived neurospheroids, the system is scalable and compatible with high-content imaging. Although it does not model BBB-specific transport mechanisms, it provides a robust framework for hypothesis-driven studies of neurovascular interactions and therapeutic screening applications.

Indexed as

Alzheimer DiseaseBlood-Brain BarrierEndothelial CellsMicrofluidicsModels, BiologicalNeural Stem CellsNeuronsAmyloid beta-PeptidesAnimalsHumansMicrophysiological SystemsPhosphorylationtau ProteinsTight JunctionsAmyloid beta-Peptidestau ProteinsAlzheimer’s disease (AD)endothelial barrierendothelial cells (ECs)microfluidicsneurospheroid

Identifiers

PMID41776543
PMCPMC13077919

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

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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.