Effect of age and the APOE gene on metabolite concentrations in the posterior cingulate cortex.
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.
Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom. Electronic address: sana.suri@psych.ox.ac.uk.
Sana
S
Suri
Functional Magnetic Resonance Imaging of the Brain Centre, University of Oxford, Oxford OX3 9DU, United Kingdom.
Uzay
U
Emir
Functional Magnetic Resonance Imaging of the Brain Centre, University of Oxford, Oxford OX3 9DU, United Kingdom.
Charlotte J
CJ
Stagg
Douglas Mental Health University Institute and Department of Psychiatry, McGill University, Montreal, Canada H4H 1R3.
Jamie
J
Near
Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Berlin, Germany; Center for Stroke Research, Berlin (CSB), Charité - Universitätsmedizin Berlin, Berlin, Germany.
Ralf
R
Mekle
Physikalisch-Technische Bundesanstalt (PTB), Braunschweig, Berlin, Germany.
Florian
F
Schubert
Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.
Enikő
E
Zsoldos
Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.
Abda
A
Mahmood
Centre for Research in Epidemiology and Population Health, INSERM, U1018 Villejuif, France.
Archana
A
Singh-Manoux
Department of Epidemiology and Public Health, University College London, United Kingdom.
Mika
M
Kivimäki
Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.
Klaus P
KP
Ebmeier
Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.
Clare E
CE
Mackay
Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.
Nicola
N
Filippini
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D053327:Apolipoprotein E4 / Q000235:genetics*; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D066244:Proton Magnetic Resonance Spectroscopy; D055815:Young Adult
D053327:Apolipoprotein E4
APOE gene; Aging; Magnetic resonance spectroscopy; Metabolites; Posterior cingulate cortex; Precuneus