Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jan 23;21(1):32.
doi: 10.1186/s12974-024-03024-8.

Modeling the neuroimmune system in Alzheimer's and Parkinson's diseases

Wendy Balestri  1   2 , Ruchi Sharma  3   4   5 , Victor A da Silva  3   4   5 , Bianca C Bobotis  4   5 , Annabel J Curle  6 , Vandana Kothakota  7 , Farnoosh Kalantarnia  3 , Maria V Hangad  4   5   8 , Mina Hoorfar  3 , Joanne L Jones  6 , Marie-Ève Tremblay  4   5   9   10   11   12   13 , Jehan J El-Jawhari  7   14 , Stephanie M Willerth  15   16   17   18 , Yvonne Reinwald  19   20
Affiliations
Review

Modeling the neuroimmune system in Alzheimer's and Parkinson's diseases

Wendy Balestri et al. J Neuroinflammation. .

Abstract

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain's resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families.

Keywords: Alzheimer’s disease; Inflammation; Modeling; Neurodegenerative diseases; Neuroimmune system; Parkinson’s disease.

PubMed Disclaimer

Conflict of interest statement

The authors have no competing financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Pathophysiology of Alzheimer’s disease and Parkinson’s disease. The schematic shows the risk factors and features associated with both disease conditions. Image created with BioRender.com
Fig. 2
Fig. 2
Comparison of healthy versus pathological neuroimmune system: in healthy neuroimmune system (1) microglia are in a homeostatic and surveillant state, (2) with limited infiltration of peripheral immune cells into the central nervous system. In the pathological neuroimmune system, (3) microglia become reactive and display an altered morphology, with increase of (4) phagocytosis, (5) inflammatory markers and (6) peripheral immune cell infiltration. Image created with BioRender.com
Fig. 3
Fig. 3
Advantages and disadvantages of in vivo and in vitro model of the neuroimmune system. The schematic shows the advantages and disadvantages of using animal models compared to cellular models, in 2D or 3D, and organ-on-a-chip. Image created with BioRender.com
Fig. 4
Fig. 4
Organ-on-a-chip development: the schematic shows the steps required for developing and fabricating a microfluidic chip. Image created with BioRender.com
See this image and copyright information in PMC

References

    1. Ghavami S, Shojaei S, Yeganeh B, Ande SR, Jangamreddy JR, Mehrpour M, et al. Autophagy and apoptosis dysfunction in neurodegenerative disorders. Prog Neurobiol. 2014;112:24–49. doi: 10.1016/j.pneurobio.2013.10.004. - DOI - PubMed
    1. Hennessy E, Griffin EW, Cunningham C. Astrocytes are primed by chronic neurodegeneration to produce exaggerated chemokine and cell infiltration responses to acute stimulation with the cytokines IL-1β and TNF-α. J Neurosci. 2015;35(22):8411–8422. doi: 10.1523/JNEUROSCI.2745-14.2015. - DOI - PMC - PubMed
    1. Vedam-Mai V. Harnessing the immune system for the treatment of Parkinson’s disease. Brain Res. 2021;1758:147308. doi: 10.1016/j.brainres.2021.147308. - DOI - PubMed
    1. Zieneldien T, Kim J, Sawmiller D, Cao C. The immune system as a therapeutic target for Alzheimer’s disease. Life. 2022;12(9):1440. doi: 10.3390/life12091440. - DOI - PMC - PubMed
    1. Erkkinen MG, Kim MO, Geschwind MD. Clinical neurology and epidemiology of the major neurodegenerative diseases. Cold Spring Harb Perspect Biol. 2017;10(4):a033118. doi: 10.1101/cshperspect.a033118. - DOI - PMC - PubMed