APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern

Shannon L Risacher; Sungeun Kim; Kwangsik Nho; Tatiana Foroud; Li Shen; Ronald C Petersen; Clifford R Jack Jr; Laurel A Beckett; Paul S Aisen; Robert A Koeppe; William J Jagust; Leslie M Shaw; John Q Trojanowski; Michael W Weiner; Andrew J Saykin; Alzheimer's Disease Neuroimaging Initiative (ADNI)

doi:10.1016/j.jalz.2015.03.003

APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern

Alzheimers Dement. 2015 Dec;11(12):1417-1429. doi: 10.1016/j.jalz.2015.03.003. Epub 2015 May 7.

Authors

Shannon L Risacher¹, Sungeun Kim², Kwangsik Nho², Tatiana Foroud³, Li Shen², Ronald C Petersen⁴, Clifford R Jack Jr⁵, Laurel A Beckett⁶, Paul S Aisen⁷, Robert A Koeppe⁸, William J Jagust⁹, Leslie M Shaw¹⁰, John Q Trojanowski¹⁰, Michael W Weiner¹¹, Andrew J Saykin¹²; Alzheimer's Disease Neuroimaging Initiative (ADNI)

Affiliations

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.

Keywords: ADNI; APOE; Alzheimer's Disease Neuroimaging Initiative; Apolipoprotein E; CSF; Cerebrospinal fluid; FDG; Neuroimaging; PET; SCD; SMC; Significant memory concern; Structural magnetic resonance imaging (MRI); Subjective cognitive decline; [(18)F]Florbetapir PET; [(18)F]Fluorodeoxyglucose.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Aged
Aged, 80 and over
Alzheimer Disease* / cerebrospinal fluid
Alzheimer Disease* / metabolism
Alzheimer Disease* / pathology
Amyloid beta-Peptides / cerebrospinal fluid*
Apolipoprotein E4 / genetics*
Biomarkers / cerebrospinal fluid
Brain / metabolism*
Brain / pathology
Cognitive Dysfunction / cerebrospinal fluid
Cognitive Dysfunction / diagnosis
Female
Genotype
Healthy Volunteers
Heterozygote
Humans
Magnetic Resonance Imaging
Male
Memory / physiology*
Neuropsychological Tests
Positron-Emission Tomography
tau Proteins / cerebrospinal fluid*

Substances

Amyloid beta-Peptides
Apolipoprotein E4
Biomarkers
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding