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Cerebral myo-inositol and glutamate+glutamine levels assessed by magnetic resonance spectroscopy in healthy aging1Neurology, Emory University, Atlanta, GA, United States, 2Physics and astronomy, Georgia State University, Atlanta, GA, United States, 3Radiology and Imaging Sciences, Emory University, Atlanta, GA, United States, 4Joint Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, United States
Synopsis
This study aims at measuring the effect of aging and expression of protein amyloid-beta (Aβ) on markers of neuroinflammation and glutamate metabolism using magnetic resonance spectroscopy. Measures of medial frontal cortical myo-inositol (mI) and glutamate+glutamine (Glx) were obtained in 21 young adults, 21 healthy older adults and 10 healthy older adults expressing Aβ. Results show an increase in mI in all older adults compared to young adults, and a decrease in Glx in all older adults compared to young adults. These results suggest that MRS is a viable tool in the investigation of biomarkers of inflammation in aging.
Introduction
Deposition of amyloid-beta (Aβ) plaques in the brain is a hallmark of Alzheimer’s disease (AD). It is believed that Aβ partakes in triggering a neuroinflammatory response which could differentiate the neurological profile in healthy older adults from older adults with positive Aβ biomarker profile. Therefore, measurement of an in vivo biomarker of neuroinflammation could provide new insight into disease cascade in AD and for its early diagnosis and prediction.Myo-inositol (mI) is a compound frequently associated with neuroinflammation and glial cell proliferation; previous studies suggest that it increases with normal aging1 and in AD2. Its measurement could provide a biomarker for neuroinflammation. Moreover, Glutamate+glutamine (Glx) is an index characterizing glutamate metabolism, which is decreased in normal aging3. We sought to investigate levels of mI and Glx using magnetic resonance spectroscopy (MRS) in healthy young adults (HY), healthy older adults with (HOAβ) and without (HO) positive Aβ biomarker in their cerebrospinal fluid. We aimed to study 1) the effect of age and 2) the effect of Aβ on the concentration levels of mI and Glx.Methods
Participants: We acquired data from 21 HY (age 25.9±3.02 years), 21 HO (age 62.6±5.17 years) and 10 HOAβ (age 69.4±8.55 years) (N =52). Informed consent was obtained from all participants, who were enrolled in the ongoing Emory Brain Imaging Project, a component of the Emory Healthy Brain Study.
Magnetic Resonance Spectroscopy (MRS): The imaging was performed on a 3T MRI system (Siemens, Prisma) with a 32 channel head coil. We acquired MRS spectra using PRESS and MEGAPRESS sequences from a 3x3x3cm voxel positioned in the MFC, superior to the genu of the corpus callosum and aligned with the shape of the corpus callosum (Figure 1). Concentration levels of mI and Glx were estimated with LC Model (see Figure 2 for an example). Segmentation of the 3D T1-weighted images was performed with SPM 12 to obtain gray matter vs white matter tissue fractions in the volume of interest of MRS scan for partial volume correction.
Statistical analyses: One-way ANOVA analyses were performed to detect differences in the metabolites with Group (HY, HO, and HOAβ) as main factor. LSD Post-hoc comparisons.
Results
ANOVA showed significant difference in the concentration of ml between the three groups (P<0.001). Post-hoc analysis showed that concentration of mI was higher in HO (P<0.001) and HOAβ (P<0.001) compared to HY (means ± standard deviations: HY 6.41 ± 0.70; HO 7.73 ± 1.34; HOAβ 7.98 ± 0.85). No significant difference was found between HO and HOAβ (P=0.896). ANOVA showed significant difference in the concentration of Glx between the three groups (P=0.001). Post-hoc analysis showed that the concentration of Glx was significantly higher in HY compared to HO (P=0.003) and HOAβ (P=0.009) (means ± standard deviations: HY 11.5 ± 1.53; HO 9.86 ± 1.53; HOAβ 9.78 ± 1.63) (Figure 3).Discussion
These preliminary results show that expression of mI increases and that of Glx decreases with aging. Importantly, they support the idea of an elevation of neuroinflammation in healthy older adults and decrease in glutamatergic metabolism. Although the comparisons between HO and HOAβ do not reach statistical significance, we believe this trend should be investigated with a larger sample size, which is an ongoing effort of our project.Conclusion
Identifying biomarkers impacted by expression of AB is critical in early AD diagnosis in healthy older adults and in the broad understanding of AD. These results suggest that MRS is a viable tool in the investigation of biomarkers depicting aging and AD.Acknowledgements
No acknowledgement found.References
1. Boumezbeur, F., Mason, G. F., de Graaf, R. A., Behar, K. L., Cline, G. W., Shulman, G. I., Petersen, K. F. (2010). Altered Brain Mitochondrial Metabolism in Healthy Aging as Assessed by in vivo Magnetic Resonance Spectroscopy. Journal of Cerebral Blood Flow & Metabolism, 30(1), 211–221.
2. Zhu, X., Schuff, N., Kornak, J., Soher, B., Yaffe, K., Kramer, J. H., Ezekiel, F., Miller, B. L., Jagust, W. J., Weiner, M. W. (2006). Effects of Alzheimer disease on fronto-parietal brain N-acetyl aspartate and myo-inositol using magnetic resonance spectroscopic imaging. Alzheimer disease and associated disorders, 20(2), 77-85.
3. MarjaĊska, M., McCarten J.R., Hodges J., Hemmy L.S., Grant A., Deelchand D.K., Terpstra M. (2017). Region-specific aging of the human brain as evidenced by neurochemical profiles measured noninvasively in the posterior cingulate cortex and the occipital lobe using 1H magnetic resonance spectroscopy at 7 T. Neuroscience, 354,168-177.
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