title: APOE genotype modulates proton magnetic resonance spectroscopy metabolites in the aging brain.
abstract: BACKGROUND
  Proton magnetic resonance spectroscopy ((1)H-MRS) studies on healthy aging have reported inconsistent findings and have not systematically taken into account the possible modulatory effect of APOE genotype. We aimed to quantify brain metabolite changes in healthy subjects in relation to age and the presence of the APOE E4 genetic risk factor for Alzheimer's disease. Additionally, we examined these measures in relation to cognition.
  
  
  METHODS
  We studied a cohort of 112 normal adults between 50 and 86 years old who were genotyped for APOE genetic polymorphism. Measurements of (1)H-MRS metabolites were obtained in the posterior cingulate and precuneus region. Measures of general cognitive functioning, memory, executive function, semantic fluency, and speed of processing were also obtained.
  
  
  RESULTS
  General linear model analysis demonstrated that older APOE E4 carriers had significantly higher choline/creatine and myo-inositol/creatine ratios than APOE E3 homozygotes. Structural equation modeling resulted in a model with an excellent goodness of fit and in which the APOE × age interaction and APOE status each had a significant effect on (1)H-MRS metabolites (choline/creatine and myo-inositol/creatine). Furthermore, the APOE × age variable modulation of cognition was mediated by (1)H-MRS metabolites.
  
  
  CONCLUSIONS
  In a healthy aging normal population, choline/creatine and myo-inositol/creatine ratios were significantly increased in APOE E4 carriers, suggesting the presence of neuroinflammatory processes and greater membrane turnover in older carriers. Structural equation modeling analysis confirmed these possible neurodegenerative markers and also indicated the mediator role of these metabolites on cognitive performance among older APOE E4 carriers.
authors.affiliation: Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, New York; FIDMAG Hermanas Hospitalarias, Sant Boi de Llobregat, Spain.
authors.forename: Jesus J
authors.initials: JJ
authors.lastname: Gomar
authors.affiliation: Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, New York; Hofstra North Shore Long Island Jewish School of Medicine, Hempstead, New York.
authors.forename: Marc L
authors.initials: ML
authors.lastname: Gordon
authors.affiliation: National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
authors.forename: Dwight
authors.initials: D
authors.lastname: Dickinson
authors.affiliation: Department of Radiology, North Shore University Hospital, Manhasset, New York.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Kingsley
authors.affiliation: Hofstra North Shore Long Island Jewish School of Medicine, Hempstead, New York; Susan and Leonard Feinstein Center for Neurosciences, The Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Aziz M
authors.initials: AM
authors.lastname: Uluğ
authors.affiliation: Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Lynda
authors.initials: L
authors.lastname: Keehlisen
authors.affiliation: Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Sarah
authors.initials: S
authors.lastname: Huet
authors.affiliation: Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Buthorn
authors.affiliation: Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, New York; Hofstra North Shore Long Island Jewish School of Medicine, Hempstead, New York.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Koppel
authors.affiliation: Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Erica
authors.initials: E
authors.lastname: Christen
authors.affiliation: Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Concepcion
authors.initials: C
authors.lastname: Conejero-Goldberg
authors.affiliation: Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, New York; Hofstra North Shore Long Island Jewish School of Medicine, Hempstead, New York.
authors.forename: Peter
authors.initials: P
authors.lastname: Davies
authors.affiliation: Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, New York; Hofstra North Shore Long Island Jewish School of Medicine, Hempstead, New York. Electronic address: tgoldber@nshs.edu.
authors.forename: Terry E
authors.initials: TE
authors.lastname: Goldberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D053318:Apolipoprotein E3 / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D007294:Inositol / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008606:Mental Processes / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D011522:Protons
chemical_list: D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D011522:Protons; D007294:Inositol; D003401:Creatine; D002794:Choline
keywords: APOE genotype; Aging; cognitive function; neurodegeneration; proton magnetic resonance spectroscopy; structural equation modeling