Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Creating a roadmap to fast-track human-centric non-animal methodologies via innovative funding mechanisms and strategic partnerships.

ALTEX·2026
Same author

Challenges and solutions in measuring commonly used biomarkers for drug-induced liver injury in a liver-on-a-chip platform.

Toxicology letters·2025
Same author

Hepatotoxicity evaluation of cannabidiol, cannabinol, cannabichromene and cannabigerol using a human quad culture liver chip.

Scientific reports·2025
Same author

Biology-inspired dynamic microphysiological system approaches to revolutionize basic research, healthcare and animal welfare.

ALTEX·2025
Same author

Role of standards and funding in accelerating the development and use of microphysiological systems.

ALTEX·2024
Same author

Modeling memory B cell responses in a lymphoid organ-chip to evaluate mRNA vaccine boosting.

The Journal of experimental medicine·2024

Related Experiment Video

Updated: Jul 10, 2026

Fabrication of Amyloid-β-Secreting Alginate Microbeads for Use in Modelling Alzheimer's Disease
06:52

Fabrication of Amyloid-β-Secreting Alginate Microbeads for Use in Modelling Alzheimer's Disease

Published on: July 6, 2019

9.7K

Modeling neurovascular dysfunction in Alzheimer's disease using an isogenic brain-chip model.

Andrew N Shen1, Katelin S Matazel1, W Drew Gill1

  • 1Division of Neurotoxicology, National Center for Toxicological Research/Food and Drug Administration, Jefferson, AR, 72079, USA.

Fluids and Barriers of the CNS
|January 6, 2026
PubMed
Summary

This study developed a brain-chip model using human cells to investigate Alzheimer's Disease (AD) pathology. The model revealed neuroinflammation and vascular tau accumulation as key factors in neurovascular unit dysfunction, independent of amyloid beta.

Keywords:
Alzheimer’s diseaseBlood-brain barrierDisease modelingHuman induced pluripotent stem cellsNeurovascular unitOrgan-chips

More Related Videos

Author Spotlight: Stimulation-Based Approach to Improve Cerebral Blood Flow in Alzheimer's Model
06:34

Author Spotlight: Stimulation-Based Approach to Improve Cerebral Blood Flow in Alzheimer's Model

Published on: June 2, 2023

1.7K
A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
05:12

A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis

Published on: November 22, 2024

1.3K

Related Experiment Videos

Last Updated: Jul 10, 2026

Fabrication of Amyloid-β-Secreting Alginate Microbeads for Use in Modelling Alzheimer's Disease
06:52

Fabrication of Amyloid-β-Secreting Alginate Microbeads for Use in Modelling Alzheimer's Disease

Published on: July 6, 2019

9.7K
Author Spotlight: Stimulation-Based Approach to Improve Cerebral Blood Flow in Alzheimer's Model
06:34

Author Spotlight: Stimulation-Based Approach to Improve Cerebral Blood Flow in Alzheimer's Model

Published on: June 2, 2023

1.7K
A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
05:12

A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis

Published on: November 22, 2024

1.3K

Area of Science:

  • Neuroscience
  • Biotechnology

Background:

  • Alzheimer's Disease (AD) pathology involves amyloid beta (Aβ) plaques and tau tangles.
  • Neurovascular dysfunction, including increased blood-brain barrier (BBB) permeability and reduced Aβ clearance, are early AD markers.
  • Current treatments for AD dementia are limited, necessitating novel therapeutic approaches and advanced in-vitro models.

Purpose of the Study:

  • To develop and utilize a novel New Alternative Method (NAM) brain-chip model.
  • To investigate neurovascular unit (NVU) dysfunction in Alzheimer's Disease using patient-derived cells.
  • To evaluate AD-like pathology and its impact on NVU function in a human induced pluripotent stem cell (hiPSC)-based model.

Main Methods:

  • A brain-chip model of the cortical neurovascular unit (NVU) was created using hiPSCs from an AD patient and a healthy individual.
  • Neurons, astrocytes, pericytes, microglia, and brain microvascular endothelial cells were differentiated and cultured in a microphysiological system.
  • The model was used to assess NVU-related endpoints, including barrier integrity, transporter activity, protein levels, and inflammatory markers.

Main Results:

  • AD brain-chips exhibited reduced claudin-5 and ZO-1 expression, increased paracellular permeability, and decreased P-glycoprotein (P-gp) activity.
  • Aβ42 levels were decreased in the brain channel, while tau and phosphorylated tau (p-tau 181) increased in the vascular channel of AD brain-chips.
  • Proinflammatory markers IL-6 and MCP-1 were elevated in both brain and vascular channels of the AD brain-chips.

Conclusions:

  • The brain-chip model demonstrated Aβ-independent NVU dysfunction linked to neuroinflammation and vascular tau accumulation.
  • This study validates the brain-chip model for evaluating AD-related NVU changes and highlights donor-specific responses in hiPSC models.
  • The findings suggest potential therapeutic targets related to neuroinflammation and vascular tau in Alzheimer's Disease.