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Neuroprotective effect of TREM-2 in aging and Alzheimer's disease model

Raha, A.A., Henderson, J.W., Stott, S.R.W., Vuono, R., Foscarin, S., Friedland, R.P., Zaman, S.H., Raha-Chowdhury, R. (2017) Neuroprotective effect of TREM-2 in aging and Alzheimer's disease model. Journal of Alzheimer's Disease, 55 (1). pp. 199-217. ISSN 1387-2877. (doi:10.3233/JAD-160663) (KAR id:79837)

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http://dx.doi.org/10.3233/JAD-160663

Abstract

Neuroinflammation and activation of innate immunity are early events in neurodegenerative diseases including Alzheimer's disease (AD). Recently, a rare mutation in the gene Triggering receptor expressed on myeloid cells 2 (TREM2) has been associated with a substantial increase in the risk of developing late onset AD. To uncover the molecular mechanisms underlying this association, we investigated the RNA and protein expression of TREM2 in APP/PS1 transgenic mice. Our findings suggest that TREM2 not only plays a critical role in inflammation, but is also involved in neuronal cell survival and in neurogenesis. We have shown that TREM2 is a soluble protein transported by macrophages through ventricle walls and choroid plexus, and then enters the brain parenchyma via radial glial cells. TREM2 protein is essential for neuroplasticity and myelination. During the late stages of life, a lack of TREM2 protein may accelerate aging processes and neuronal cell loss and reduce microglial activity, ultimately leading to neuroinflammation. As inflammation plays a major role in neurodegenerative diseases, a lack of TREM2 could be a missing link between immunomodulation and neuroprotection.

Item Type: Article
DOI/Identification number: 10.3233/JAD-160663
Uncontrolled keywords: lipopolysaccharide; triggering receptor expressed on myeloid cells 2; amyloid precursor protein; APP protein, human; immunoglobulin receptor; membrane protein; messenger RNA; presenilin 1; PSEN1 protein, human, aging; Alzheimer disease; animal cell; animal experiment; animal model; animal tissue; Article; brain tissue; cell survival; choroid plexus; controlled study; disease course; disease model; endosome; glia cell; Golgi complex; heart ventricle wall motion; macrophage; mouse; myelination; nerve cell; nerve cell plasticity; nervous system development; neuroprotection; nonhuman; parenchyma; priority journal; protein expression; Alzheimer disease; animal; brain; C57BL mouse; cell culture; genetics; human; meninx; metabolism; microglia; neuroprotection; pathology; physiology; Sprague Dawley rat; transgenic mouse, Aging; Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Brain; Cells, Cultured; Humans; Lipopolysaccharides; Macrophages; Membrane Glycoproteins; Meninges; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Neurogenesis; Neurons; Neuroprotection; Presenilin-1; Rats, Sprague-Dawley; Receptors, Immunologic; RNA, Messenger
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Romina Vuono
Date Deposited: 29 Jan 2020 10:36 UTC
Last Modified: 16 Feb 2021 14:11 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/79837 (The current URI for this page, for reference purposes)
Vuono, R.: https://orcid.org/0000-0002-5162-3422
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