Shannon L Risacher1, Sungeun Kim2, Kwangsik Nho2, Tatiana Foroud3, Li Shen2, Ronald C Petersen4, Clifford R Jack5, Laurel A Beckett6, Paul S Aisen7, Robert A Koeppe8, William J Jagust9, Leslie M Shaw10, John Q Trojanowski10, Michael W Weiner11, Andrew J Saykin12. 1. Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA. 2. Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA. 3. Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. 4. Department of Neurology, Mayo Clinic, Rochester MN, USA. 5. Department of Radiology, Mayo Clinic, Rochester MN, USA. 6. Department of Public Health Sciences, Division of Biostatistics, University of California-Davis, Davis, CA, USA. 7. Department of Neurology, University of California-San Diego, San Diego, CA, USA. 8. Department of Radiology, University of Michigan, Ann Arbor, MI, USA. 9. Department of Neurology, University of California-Berkeley, Berkeley, CA, USA. 10. Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. 11. Departments of Radiology, Medicine and Psychiatry, University of California-San Francisco, San Francisco, CA, USA; Department of Veterans Affairs Medical Center, San Francisco, CA, USA. 12. Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA; Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: asaykin@iupui.edu.
Abstract
INTRODUCTION: This study assessed apolipoprotein E (APOE) ε4 carrier status effects on Alzheimer's disease imaging and cerebrospinal fluid (CSF) biomarkers in cognitively normal older adults with significant memory concerns (SMC). METHODS: Cognitively normal, SMC, and early mild cognitive impairment participants from Alzheimer's Disease Neuroimaging Initiative were divided by APOE ε4 carrier status. Diagnostic and APOE effects were evaluated with emphasis on SMC. Additional analyses in SMC evaluated the effect of the interaction between APOE and [(18)F]Florbetapir amyloid positivity on CSF biomarkers. RESULTS: SMC ε4+ showed greater amyloid deposition than SMC ε4-, but no hypometabolism or medial temporal lobe (MTL) atrophy. SMC ε4+ showed lower amyloid beta 1-42 and higher tau/p-tau than ε4-, which was most abnormal in APOE ε4+ and cerebral amyloid positive SMC. DISCUSSION: SMC APOE ε4+ show abnormal changes in amyloid and tau biomarkers, but no hypometabolism or MTL neurodegeneration, reflecting the at-risk nature of the SMC group and the importance of APOE in mediating this risk.
INTRODUCTION: This study assessed apolipoprotein E (APOE) ε4 carrier status effects on Alzheimer's disease imaging and cerebrospinal fluid (CSF) biomarkers in cognitively normal older adults with significant memory concerns (SMC). METHODS: Cognitively normal, SMC, and early mild cognitive impairmentparticipants from Alzheimer's Disease Neuroimaging Initiative were divided by APOE ε4 carrier status. Diagnostic and APOE effects were evaluated with emphasis on SMC. Additional analyses in SMC evaluated the effect of the interaction between APOE and [(18)F]Florbetapir amyloid positivity on CSF biomarkers. RESULTS: SMC ε4+ showed greater amyloid deposition than SMC ε4-, but no hypometabolism or medial temporal lobe (MTL) atrophy. SMC ε4+ showed lower amyloid beta 1-42 and higher tau/p-tau than ε4-, which was most abnormal in APOE ε4+ and cerebral amyloid positive SMC. DISCUSSION: SMC APOE ε4+ show abnormal changes in amyloid and tau biomarkers, but no hypometabolism or MTL neurodegeneration, reflecting the at-risk nature of the SMC group and the importance of APOE in mediating this risk.
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