Decreased γ-aminobutyric acid levels in the parietal region of patients with Alzheimer's disease

Abstract

Purpose: To determine whether there are in vivo differences of γ-aminobutyric acid (GABA) levels in frontal and parietal regions of Alzheimer's disease (AD) patients, compared with healthy controls using magnetic resonance spectroscopy ((1) H-MRS).

Materials and methods: Fifteen AD patients and fifteen age- and gender-matched healthy controls underwent (1) H-MRS of the frontal and parietal lobes using the "MEGA-Point Resolved Spectroscopy Sequence" (MEGA-PRESS) technique, and cognitive levels of subjects were evaluated using Mini-Mental State Examination (MMSE) tests. MRS data were processed using the Gannet program. Because the signal detected by MEGA-PRESS includes contributions from GABA, macromolecules and homocarnosine, it is labeled as "GABA+" rather than GABA. Differences of GABA+/Cr ratios between AD patients and controls were tested using covariance analysis, adjusting for gray matter fraction. The relationship between GABA+/Cr and MMSE scores was also analyzed.

Results: Significant lower GABA+/Cr ratios were found in the parietal region of AD patients compared with controls (P = 0.041). In AD patients, no significant correlations between GABA+/Cr and MMSE scores were found in either the frontal (r = -0.164; P = 0.558) or parietal regions (r = 0.025; P = 0.929).

Conclusion: Decreased GABA+/Cr levels were present in the parietal region of patients with AD in vivo, suggesting that abnormalities of the GABAergic system may be present in the pathogenesis of AD.

Keywords: 1H-MRS; Alzheimer's disease; GABA; MEGA-PRESS; MMSE.

Figure 1

The position of voxels, corresponding segmentation data and representative spectra. The (a,d) and (b,e) panels show the position of volumes of interest in frontal (upper) and parietal regions (lower) on sagittal and coronal T1-weighted TFE images in an AD patient. The corresponding results of brain segmentation are shown in the frontal (c) and parietal regions (f). (g, h) Show the representative MEGA-PRESS spectra processed using the “Gannet 2.0” toolkit in frontal and parietal regions of AD. (g) Shows the curve-fitting of the GABA peak using Gannet, the red lines in the panels are the results of the GannetFit curve-fitting, the blue lines show the postphase and frequency aligned GABA data, and the black line is the residual difference between the experimental data and the curve-fit. (h) is the MEGA-PRESS difference spectrum. The Glx, GABA and MM peaks resonate at 3.7, 3.0 ppm and 0.9 ppm respectively.

Figure 2

The GABA+/Cr ratios of AD patients and HC in frontal (a) and parietal (b) regions. The mean and standard deviation of GABA+/Cr ratios are displayed. a: Shows that the mean GABA+/Cr ratios are lower in AD than in HC in frontal region (P = 0.345), but no statistical difference is detected. There does appear to be one “outlier” value in the control group, however, no significant differences are found in this region between AD and HC, whether this point is included or not. b: Shows GABA+/Cr ratios of AD group are significantly decreased in the parietal region (P = 0.041).