Effect of age and the APOE gene on metabolite concentrations in the posterior cingulate cortex.
Suri S., Emir U., Stagg CJ., Near J., Mekle R., Schubert F., Zsoldos E., Mahmood A., Singh-Manoux A., Kivimäki M., Ebmeier KP., Mackay CE., Filippini N.
Proton magnetic resonance spectroscopy (1H-MRS) has provided valuable information about the neurochemical profile of Alzheimer's disease (AD). However, its clinical utility has been limited in part by the lack of consistent information on how metabolite concentrations vary in the normal aging brain and in carriers of apolipoprotein E (APOE) ε4, an established risk gene for AD. We quantified metabolites within an 8cm3voxel within the posterior cingulate cortex (PCC)/precuneus in 30 younger (20-40 years) and 151 cognitively healthy older individuals (60-85 years). All1H-MRS scans were performed at 3T using the short-echo SPECIAL sequence and analyzed with LCModel. The effect of APOE was assessed in a sub-set of 130 volunteers. Older participants had significantly higher myo-inositol and creatine, and significantly lower glutathione and glutamate than younger participants. There was no significant effect of APOE or an interaction between APOE and age on the metabolite profile. Our data suggest that creatine, a commonly used reference metabolite in1H-MRS studies, does not remain stable across adulthood within this region and therefore may not be a suitable reference in studies involving a broad age-range. Increases in creatine and myo-inositol may reflect age-related glial proliferation; decreases in glutamate and glutathione suggest a decline in synaptic and antioxidant efficiency. Our findings inform longitudinal clinical studies by characterizing age-related metabolite changes in a non-clinical sample.