Alzheimer's disease (AD) is a progressive disorder associated with disruption of neuronal function and neuronal loss. N-acetylaspartate (NAA) is a marker of neuronal content and can be assessed using proton (1H) magnetic resonance spectroscopy (MRS). We utilized 1H-MRS (two-dimensional chemical-shift imaging) to assess amplitudes and areas of NAA, as well as choline moieties (Cho), creatine (Cr) and myo-inositol (mI), in 15 AD patients compared with 14 control subjects. Voxels were classified as predominantly cortical gray matter (CGM), subcortical gray matter (SGM), or white matter (WM). Compared with control subjects, AD patients exhibited decreased NAA/Cho and NAA/Cr amplitudes, whereas an increase was observed in Cho/Cr and in amplitude ratios involving mI. Area ratios were significant in the same direction for NAA/Cho, NAA/Cr, mI/Cr and mI/NAA. No significant effects of tissue type were observed; however, significant group x tissue type interactions were noted for Cho/Cr and mI/Cr amplitudes. Our study confirms that 1H-MRS can identify distinct physicochemical alterations in AD patients, reflecting membrane changes and diminished neuronal function. These alterations can be used as longitudinal markers for the disease.