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A 3D human brain-like tissue model of herpes-induced Alzheimer's disease.
Sci Adv. 2020 May; 6(19):eaay8828.SA

Abstract

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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Authors+Show Affiliations

Cairns DM
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA. Allen Discovery Center, Tufts University, Medford, MA 02155, USA.
Rouleau N
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA. Allen Discovery Center, Tufts University, Medford, MA 02155, USA.
Parker RN
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Walsh KG
Department of Biology, Tufts University, Medford, MA 02155, USA.
Gehrke L
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Kaplan DL
Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA. Allen Discovery Center, Tufts University, Medford, MA 02155, USA.

MeSH

Alzheimer DiseaseAmyloid beta-PeptidesBrainGliosisHerpes SimplexHerpesvirus 1, HumanHumansPlaque, Amyloid

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32494701

Citation

Cairns, Dana M., et al. "A 3D Human Brain-like Tissue Model of Herpes-induced Alzheimer's Disease." Science Advances, vol. 6, no. 19, 2020, pp. eaay8828.
Cairns DM, Rouleau N, Parker RN, et al. A 3D human brain-like tissue model of herpes-induced Alzheimer's disease. Sci Adv. 2020;6(19):eaay8828.
Cairns, D. M., Rouleau, N., Parker, R. N., Walsh, K. G., Gehrke, L., & Kaplan, D. L. (2020). A 3D human brain-like tissue model of herpes-induced Alzheimer's disease. Science Advances, 6(19), eaay8828. https://doi.org/10.1126/sciadv.aay8828
Cairns DM, et al. A 3D Human Brain-like Tissue Model of Herpes-induced Alzheimer's Disease. Sci Adv. 2020;6(19):eaay8828. PubMed PMID: 32494701.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A 3D human brain-like tissue model of herpes-induced Alzheimer's disease. AU - Cairns,Dana M, AU - Rouleau,Nicolas, AU - Parker,Rachael N, AU - Walsh,Katherine G, AU - Gehrke,Lee, AU - Kaplan,David L, Y1 - 2020/05/06/ PY - 2019/7/25/received PY - 2020/2/18/accepted PY - 2020/6/5/entrez PY - 2020/6/5/pubmed PY - 2022/4/9/medline PY - 2020/5/6/pmc-release SP - eaay8828 EP - eaay8828 JF - Science advances JO - Sci Adv VL - 6 IS - 19 N2 - 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. SN - 2375-2548 UR - https://www.unboundmedicine.com/medline/citation/32494701/full_citation DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓129 ↑60]

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