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Increase of TREM2 during Aging of an Alzheimer’s Disease Mouse Model Is Paralleled by Microglial Activation and Amyloidosis

Front Neuroanat. 2017 Jan 20;10:127. doi: 10.3389/fnana.2016.00127. eCollection 2016.

Authors/Editors: Brendel M, Kleinberger G, Probst F, Jaworska A, Overhoff F, Blume T, Albert NL, Carlsen J, Lindner S, Gildehaus FJ, Ozmen L, Suárez-Calvet M, Bartenstein P, Baumann K, Ewers M, Haass C, Herms J, Rominger A.
Publication Date: 2017

2017_01_brendel

Abstract

Heterozygous missense mutations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been reported to significantly increase the risk of developing Alzheimer’s disease (AD). Since TREM2 is specifically expressed by microglia in the brain, we hypothesized that soluble TREM2 (sTREM2) levels may increase together with in vivo biomarkers of microglial activity and amyloidosis in an AD mouse model as assessed by small animal positron-emission-tomography (mPET). In this crosssectional study, we examined a strong amyloid mouse model (PS2APP) of four age groups by mPET with [18F]-GE180 (glial activation) and [18F]-florbetaben (amyloidosis), followed by measurement of sTREM2 levels and amyloid levels in the brain. Pathology affected brain regions were compared between tracers (dice similarity coefficients) and pseudo-longitudinally. mPET results of both tracers were correlated with terminal TREM2 levels. The brain sTREM2 levels strongly increased with age of PS2APP mice (5 vs. 16 months: +211%, p < 0.001), and correlated highly with mPET signals of microglial activity (R = 0.89, p < 0.001) and amyloidosis (R = 0.92, p < 0.001). Dual mPET enabled regional mapping of glial activation and amyloidosis in the mouse brain, which progressed concertedly leading to a high overlap in aged PS2APP mice (dice similarity 67%). Together, these results substantiate the use of in vivo mPET measurements in conjunction with post mortem sTREM2 in future anti-inflammatory treatment trials. Taking human data into account sTREM2 may increase during active amyloid deposition.

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