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
. 2021 Apr 26:13:665612.
doi: 10.3389/fnagi.2021.665612. eCollection 2021.

Association Between sTREM2, an Immune Biomarker of Microglial Activation, and Aging-Related Brain Volume Changes in Community-Dwelling Older Adults: A 7-Year Follow-Up Study

Ryuzo Orihashi  1 , Yoshito Mizoguchi  1 , Yoshiomi Imamura  1 , Shigeto Yamada  2 , Akira Monji  1
Affiliations

Association Between sTREM2, an Immune Biomarker of Microglial Activation, and Aging-Related Brain Volume Changes in Community-Dwelling Older Adults: A 7-Year Follow-Up Study

Ryuzo Orihashi et al. Front Aging Neurosci. .

Abstract

Background: This study aimed to investigate the association between serum levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble form of an innate immune receptor expressed on the microglia, and brain volume in older adults.

Methods: The survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 596 residents. Serum sTREM2 level measurements, brain MRI, Mini-Mental State Examination (MMSE), and clinical dementia rating (CDR) were performed at Time 1 (2009-2011). Follow-up brain MRI, MMSE, and CDR were performed at Time 2 (2016-2017). The interval between Time 1 and Time 2 was approximately 7 years. Sixty-nine participants (16 men, mean age 72.69 ± 3.18 years; 53 women, mean age 72.68 ± 4.64 years) completed this study. We analyzed the correlation between serum sTREM2 levels (Time 1) and brain volume (Time 1, Time 2, and Time 1-Time 2 difference) using voxel-based morphometry implemented with Statistical Parametric Mapping.

Results: Participants in this study had lower MMSE and higher CDR scores 7 years after the baseline evaluation. However, analyses at the cluster level by applying multiple comparison corrections (family wise error; P < 0.05) showed no correlation between serum sTREM2 levels and volume of different brain regions, either cross-sectional or longitudinal.

Conclusion: Serum sTREM2 level could not serve as an immune biomarker of aging-related volume changes in brain regions closely related to cognitive function in older adults aged 65 years and above.

Keywords: MRI; brain volume; cognitive function; sTREM2; voxel-based morphometry.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart depicting selection procedure.
FIGURE 2
FIGURE 2
Voxel-based morphometry findings: Association between serum sTREM2 levels (Time 1) and brain volume (Time 2). Positive correlation between serum sTREM2 levels (Time 1) and brain volume (Time 2), as shown by multiple regression analysis. The threshold for statistics were set to T = 3.23 for the height threshold and k = 122 voxels for the extent threshold. Volumes of the important regions are shown in (A) whole brain images and (B) axial images. The T-value applies to (B) axial images.
FIGURE 3
FIGURE 3
Voxel-based morphometry findings: Association between changes in clinical dementia rating (CDR) scores and brain volume (Time 2). Association between higher CDR scores and decreased brain volume (Time 2) evaluated using multiple regression analysis. The thresholds for statistics were set to T = 3.22 for the height threshold and k = 2684 voxels for the extent threshold. Significant clusters containing the left and the right hippocampus are shown in (A) whole brain images and (B) axial images. The T-value applies to (B) axial images.
See this image and copyright information in PMC

References

    1. Ashburner J. (2007). A fast diffeomorphic image registration algorithm. Neuroimage 38 95–113. 10.1016/j.neuroimage.2007.07.007 - DOI - PubMed
    1. Ashburner J., Friston K. J. (2000). Voxel-based morphometry–the methods. Neuroimage 11 805–821. 10.1006/nimg.2000.0582 - DOI - PubMed
    1. Ashburner J., Ridgway G. R. (2012). Symmetric diffeomorphic modeling of longitudinal structural MRI. Front. Neurosci. 6:197. 10.3389/fnins.2012.00197 - DOI - PMC - PubMed
    1. Ewers M., Franzmeier N., Suárez-Calvet M., Morenas-Rodriguez E., Caballero M. A. A., Kleinberger G., et al. (2019). Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer’s disease. Sci. Transl. Med. 11:eaav6221. 10.1126/scitranslmed.aav6221 - DOI - PMC - PubMed
    1. Fink G. R., Markowitsch H. J., Reinkemeier M., Bruckbauer T., Kessler J., Heiss W. D. (1996). Cerebral representation of one’s own past: neural networks involved in autobiographical memory. J. Neurosci. 16 4275–4282. 10.1523/JNEUROSCI.16-13-04275.1996 - DOI - PMC - PubMed