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Plasma soluble TREM2 and inflammatory markers in Alzheimer’s disease
Author(s) -
Weber Grace E.,
Khrestian Maria,
Shao Yvonne,
Tuason Elizabeth D.,
Rao Stephen M.,
Pillai Jagan A.,
Leverenz James B.,
Bekris Lynn M.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.043649
Subject(s) - trem2 , cytokine , chemokine , immunology , immune system , proinflammatory cytokine , inflammation , receptor , microglia , tumor necrosis factor alpha , alzheimer's disease , disease , medicine , biology
Background Triggering receptor expressed on myeloid cells 2 (TREM2) activation is involved in several cellular functions such as cell survival, phagocytosis and cytokine production. TREM2 genetic variants have been shown to increase risk for AD and other neurodegenerative disorders. Leukocyte TREM2 mRNA has been described as elevated in AD. However, the cleaved, soluble protein (sTREM2) is not elevated in AD plasma suggesting that plasma sTREM2 is less likely to play a significant a role in AD. As TREM2 mRNA is elevated in AD, it is also possible that membrane bound TREM2 plays a more important role in AD, by inhibiting certain cytokine or chemokines. We therefore hypothesized that plasma sTREM2 positively correlates with certain plasma cytokines and chemokines in cognitively normal controls, but not in AD. Method We investigated this hypothesis in a study of adults with AD, mild cognitive impairment (MCI), and age‐matched cognitively normal controls (HC). A panel of 38 immune factors and sTREM2 were measured in plasma utilizing the Luminex platform. Hierarchical clustering and correlation analyses were used to demonstrate differing relationships between sTREM2, cytokines and chemokines in AD or MCI, compared to HC. Result We observed a relationship between plasma sTREM2 and cytokines in our cohort that varied by disease status. Conclusions Our results suggest that plasma sTREM2 is related to an aberrant peripheral inflammatory profile in AD. Increased levels of sTREM2 correlated positively with anti‐inflammatory, regulatory, and pro‐inflammatory cytokines in plasma. This study provides a basis for future studies investigating peripheral sTREM2 and the development of AD.