APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern
Abstract
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). 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 [18F]Florbetapir amyloid positivity on CSF biomarkers. 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. Lastly, 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.
- Authors:
-
- Indiana Univ., Indianapolis, IN (United States). School of Medicine, Dept. of Radiology and Imaging Sciences, Center for Neuroimaging; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Indiana Alzheimer Disease Center
- Indiana Univ., Indianapolis, IN (United States). School of Medicine, Dept. of Radiology and Imaging Sciences, Center for Neuroimaging; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Indiana Alzheimer Disease Center; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Center for Computational Biology and Bioinformatics
- Indiana Univ., Indianapolis, IN (United States). School of Medicine, Indiana Alzheimer Disease Center; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Dept. of Medical and Molecular Genetics
- Mayo Clinic, Rochester, MN (United States). Dept. of Neurology
- Mayo Clinic, Rochester, MN (United States). Dept. of Radiology
- Univ. of California, Davis, CA (United States). Dept. of Public Health Sciences, Division of Biostatistics
- Univ. of California, San Diego, CA (United States). Dept. of Neurology
- Univ. of Michigan, Ann Arbor, MI (United States). Dept. of Radiology
- Univ. of California, Berkeley, CA (United States). Dept. of Neurology
- Univ. of Pennsylvania, Philadelphia, PA (United States). School of Medicine, Dept. of Pathology and Lab. Medicine
- Univ. of California, San Francisco, CA (United States). Dept. of Radiology, Medicine and Psychiatry; Dept. of Veterans Affairs Medical Center, San Francisco, CA (United States)
- Indiana Univ., Indianapolis, IN (United States). School of Medicine, Dept. of Radiology and Imaging Sciences, Center for Neuroimaging; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Indiana Alzheimer Disease Center; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Center for Computational Biology and Bioinformatics; Indiana Univ., Indianapolis, IN (United States). School of Medicine, Dept. of Medical and Molecular Genetics
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE; National Institutes of Health (NIH)
- OSTI Identifier:
- 1378678
- Grant/Contract Number:
- AC02-05CH11231; U01 AG024904; W81XWH-12-2-0012; P30 AG010129; K01 AG030514
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Alzheimer's & Dementia
- Additional Journal Information:
- Journal Volume: 11; Journal Issue: 12; Journal ID: ISSN 1552-5260
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; Significant memory concern; SMC; Subjective cognitive decline; SCD; Apolipoprotein E; APOE; Neuroimaging; [18F]Florbetapir PET; [18F]Fluorodeoxyglucose; FDG; PET; Structural magnetic resonance imaging (MRI); Cerebrospinal fluid; CSF; Alzheimer's Disease Neuroimaging Initiative; ADNI
Citation Formats
Risacher, Shannon L., Kim, Sungeun, Nho, Kwangsik, Foroud, Tatiana, Shen, Li, Petersen, Ronald C., Jack, Clifford R., Beckett, Laurel A., Aisen, Paul S., Koeppe, Robert A., Jagust, William J., Shaw, Leslie M., Trojanowski, John Q., Weiner, Michael W., and Saykin, Andrew J. APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern. United States: N. p., 2015.
Web. doi:10.1016/j.jalz.2015.03.003.
Risacher, Shannon L., Kim, Sungeun, Nho, Kwangsik, Foroud, Tatiana, Shen, Li, Petersen, Ronald C., Jack, Clifford R., Beckett, Laurel A., Aisen, Paul S., Koeppe, Robert A., Jagust, William J., Shaw, Leslie M., Trojanowski, John Q., Weiner, Michael W., & Saykin, Andrew J. APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern. United States. https://doi.org/10.1016/j.jalz.2015.03.003
Risacher, Shannon L., Kim, Sungeun, Nho, Kwangsik, Foroud, Tatiana, Shen, Li, Petersen, Ronald C., Jack, Clifford R., Beckett, Laurel A., Aisen, Paul S., Koeppe, Robert A., Jagust, William J., Shaw, Leslie M., Trojanowski, John Q., Weiner, Michael W., and Saykin, Andrew J. Thu .
"APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern". United States. https://doi.org/10.1016/j.jalz.2015.03.003. https://www.osti.gov/servlets/purl/1378678.
@article{osti_1378678,
title = {APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern},
author = {Risacher, Shannon L. and Kim, Sungeun and Nho, Kwangsik and Foroud, Tatiana and Shen, Li and Petersen, Ronald C. and Jack, Clifford R. and Beckett, Laurel A. and Aisen, Paul S. and Koeppe, Robert A. and Jagust, William J. and Shaw, Leslie M. and Trojanowski, John Q. and Weiner, Michael W. and Saykin, Andrew J.},
abstractNote = {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). 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 [18F]Florbetapir amyloid positivity on CSF biomarkers. 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. Lastly, 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.},
doi = {10.1016/j.jalz.2015.03.003},
journal = {Alzheimer's & Dementia},
number = 12,
volume = 11,
place = {United States},
year = {Thu May 07 00:00:00 EDT 2015},
month = {Thu May 07 00:00:00 EDT 2015}
}
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- Alzheimer's Research & Therapy, Vol. 10, Issue 1
Anxiety correlates with cortical surface area in subjective cognitive decline: APOE ε4 carriers versus APOE ε4 non-carriers
journal, June 2019
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- Alzheimer's Research & Therapy, Vol. 11, Issue 1
Subjective Cognitive Decline and Alzheimer's Disease Spectrum Disorder
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Prediction of Alzheimer's Pathological Changes in Subjective Cognitive Decline Using the Self-report Questionnaire and Neuroimaging Biomarkers
journal, January 2019
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Fine-mapping of the human leukocyte antigen locus as a risk factor for Alzheimer disease: A case–control study
journal, March 2017
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The use of back propagation neural networks and 18F-Florbetapir PET for early detection of Alzheimer’s disease using Alzheimer’s Disease Neuroimaging Initiative database
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Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?
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Biomarkers for Alzheimer's Disease Diagnosis
journal, October 2017
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Subjective Cognitive Impairment in 55-65-Year-Old Adults Is Associated with Negative Affective Symptoms, Neuroticism, and Poor Quality of Life
journal, February 2019
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A Bayesian Model for the Prediction and Early Diagnosis of Alzheimer's Disease
journal, March 2017
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The Relation Between Brain Amyloid Deposition, Cortical Atrophy, and Plasma Biomarkers in Amnesic Mild Cognitive Impairment and Alzheimer’s Disease
journal, June 2018
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Prediction of Mild Cognitive Impairment Conversion Using a Combination of Independent Component Analysis and the Cox Model
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Classification of Early and Late Mild Cognitive Impairment Using Functional Brain Network of Resting-State fMRI
journal, August 2019
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The Contribution of Genetic Factors to Cognitive Impairment and Dementia: Apolipoprotein E Gene, Gene Interactions, and Polygenic Risk
journal, March 2019
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