A 3D human brain–like tissue model of herpes-induced Alzheimer’s disease
Open accessAbstract
Alzheimer's disease (AD) is a neurodegenerative disorder that causes cognitive decline, memory loss, and inability to perform everyday functions. Hallmark features of AD-including generation of amyloid plaques, neurofibrillary tangles, gliosis, and inflammation in the brain-are well defined; however, the cause of the disease remains elusive. Growing evidence implicates pathogens in AD development, with herpes simplex virus type I (HSV-1) gaining increasing attention as a potential causative agent. Here, we describe a multidisciplinary approach to produce physiologically relevant human tissues to study AD using human-induced neural stem cells (hiNSCs) and HSV-1 infection in a 3D bioengineered brain model. We report a herpes-induced tissue model of AD that mimics human disease with multicellular amyloid plaque-like formations, gliosis, neuroinflammation, and decreased functionality, completely in the absence of any exogenous mediators of AD. This model will allow for future studies to identify potential downstream drug targets for treating this devastating disease.
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In a silk protein scaffold using HSV-1, researchers mimicked plaque formation, neuroinflammation, and decreased cell functionality without exogenous AD mediators.
“They were able to mimic the plaque formation, neuroinflammation, and decreased functionality of the cells without the use of exogenous AD mediators.”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [136]
After plaque formation, the HSV-1 silk scaffold model can no longer be used to evaluate preventative strategies.
“It should be noted that after plaque formation, the model can no longer be used to evaluate preventative strategies.”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [136]
The Results describe plaque-like formation in the 3D model and antiviral treatment given at infection or one day later, while the Discussion suggests the model may help develop treatment strategies. Neither section addresses whether the model can be used to evaluate preventative strategies after plaques have formed; searches for that timing-based limitation found no passage stating it. (LLM, conf=0.72)
Experimental — accuracy not yet measuredLow-grade HSV-1 infection induced an AD-like phenotype in brain organoids derived from hiNSCs.
“This work, furthermore, showed that low-grade HSV-1 infection induced an AD-like phenotype in brain organoids derived from hiNSCs (236).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [236]
HSV-1 infection of human-induced neural stem cell lines in vitro induced gliosis and inflammation, including production of IL-1β, IL-6, and IFN-γ.
“The authors showed that infecting human-induced neural stem cell (hiNSC) lines with HSV-1 in vitro induced gliosis and inflammation, including the production of pro-inflammatory cytokines such as IL-1β, IL-6, and IFN-γ.”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [236]
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- Authors
- Cairns, D. M., Rouleau, N., Parker, R. N., Walsh, K. G., Gehrke, L., & Kaplan, D. L.
- Affiliations
- Tufts University (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Kaplan, David L.
- Venue
- Science Advances
- Published
- 2020-05-08
- Volume
- 6
- Issue
- 19
- Pages
- eaay8828-eaay8828
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC7202879
- OpenAlex
- W3023103130
- Cited by
- 247
- References
- 63
- Citations by year
- 2026: 17 · 2025: 30 · 2024: 44 · 2023: 35 · 2022: 40 · 2021: 52 · 2020: 29
- FWCI
- 23.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Science Advances (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institutes of Health (R01NS092847)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Alzheimer's disease, herpes simplex virus type 1, HSV-1 infection, amyloid plaques, gliosis, neuroinflammation
- MeSH terms
- Alzheimer Disease, Brain, Gliosis, Herpes Simplex, Humans, Amyloid beta-Peptides, Herpesvirus 1, Human, Plaque, Amyloid
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