The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI)

Shannon L. Risacher, Sungeun Kim, Li Shen, Kwangsik Nho, Tatiana Foroud, Robert C. Green, Ronald C. Petersen, Clifford R. Jack, Paul S. Aisen, Robert A. Koeppe, William J. Jagust, Leslie M. Shaw, John Q. Trojanowski, Michael W. Weiner, Andrew Saykin

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Abstract

Objective: Our goal was to evaluate the association of APOE with amyloid deposition, cerebrospinal fluid levels (CSF) of Aβ, tau, and p-tau, brain atrophy, cognition and cognitive complaints in E-MCI patients and cognitively healthy older adults (HC) in the ADNI-2 cohort. Methods: Two-hundred and nine E-MCI and 123 HC participants from the ADNI-2 cohort were included. We evaluated the impact of diagnostic status (E-MCI vs. HC) and APOE ε4 status (ε4 positive vs. ε4 negative) on cortical amyloid deposition (AV-45/Florbetapir SUVR PET scans), brain atrophy (structural MRI scans processed using voxel-based morphometry and Freesurfer version 5.1), CSF levels of Aβ, tau, and p-tau, and cognitive performance and complaints. Results: E-MCI participants showed significantly impaired cognition, higher levels of cognitive complaints, greater levels of tau and p-tau, and subcortical and cortical atrophy relative to HC participants (p < 0.05). Cortical amyloid deposition and CSF levels of Aβ were significantly associated with APOE ε4 status but not E-MCI diagnosis, with ε4 positive participants showing more amyloid deposition and lower levels of CSF Aβ than ε4 negative participants. Other effects of APOE ε4 status on cognition and CSF tau levels were also observed. Conclusions: APOE ε4 status is associated with amyloid accumulation and lower CSF Aβ, as well as increased CSF tau levels in early prodromal stages of AD (E-MCI) and HC. Alternatively, neurodegeneration, cognitive impairment, and increased complaints are primarily associated with a diagnosis of E-MCI. These findings underscore the importance of considering APOE genotype when evaluating biomarkers in early stages of disease.

Original languageEnglish
Article numberArticle 11
JournalFrontiers in Aging Neuroscience
Volume5
Issue numberAPR
DOIs
StatePublished - 2013

Fingerprint

Apolipoproteins E
Cerebrospinal Fluid
Genotype
Apolipoprotein E4
Amyloid
Cognition
Atrophy
Prodromal Symptoms
Cognitive Dysfunction
Brain
Positron-Emission Tomography
Biomarkers
Magnetic Resonance Imaging

Keywords

  • Alzheimer's disease neuroimaging initiative (ADNI)
  • Apolipoprotein E (APOE)
  • Cerebrospinal fluid (CSF)
  • Early mild cognitive impairment (E-MCI)
  • Florbetapir/AV-45/Amyvid
  • Magnetic resonance imaging (MRI)
  • Positron emission tomography (PET)

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience

Cite this

The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI). / Risacher, Shannon L.; Kim, Sungeun; Shen, Li; Nho, Kwangsik; Foroud, Tatiana; Green, Robert C.; Petersen, Ronald C.; Jack, Clifford R.; Aisen, Paul S.; Koeppe, Robert A.; Jagust, William J.; Shaw, Leslie M.; Trojanowski, John Q.; Weiner, Michael W.; Saykin, Andrew.

In: Frontiers in Aging Neuroscience, Vol. 5, No. APR, Article 11, 2013.

Research output: Contribution to journalArticle

Risacher, SL, Kim, S, Shen, L, Nho, K, Foroud, T, Green, RC, Petersen, RC, Jack, CR, Aisen, PS, Koeppe, RA, Jagust, WJ, Shaw, LM, Trojanowski, JQ, Weiner, MW & Saykin, A 2013, 'The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI)', Frontiers in Aging Neuroscience, vol. 5, no. APR, Article 11. https://doi.org/10.3389/fnagi.2013.00011
Risacher, Shannon L. ; Kim, Sungeun ; Shen, Li ; Nho, Kwangsik ; Foroud, Tatiana ; Green, Robert C. ; Petersen, Ronald C. ; Jack, Clifford R. ; Aisen, Paul S. ; Koeppe, Robert A. ; Jagust, William J. ; Shaw, Leslie M. ; Trojanowski, John Q. ; Weiner, Michael W. ; Saykin, Andrew. / The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI). In: Frontiers in Aging Neuroscience. 2013 ; Vol. 5, No. APR.
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abstract = "Objective: Our goal was to evaluate the association of APOE with amyloid deposition, cerebrospinal fluid levels (CSF) of Aβ, tau, and p-tau, brain atrophy, cognition and cognitive complaints in E-MCI patients and cognitively healthy older adults (HC) in the ADNI-2 cohort. Methods: Two-hundred and nine E-MCI and 123 HC participants from the ADNI-2 cohort were included. We evaluated the impact of diagnostic status (E-MCI vs. HC) and APOE ε4 status (ε4 positive vs. ε4 negative) on cortical amyloid deposition (AV-45/Florbetapir SUVR PET scans), brain atrophy (structural MRI scans processed using voxel-based morphometry and Freesurfer version 5.1), CSF levels of Aβ, tau, and p-tau, and cognitive performance and complaints. Results: E-MCI participants showed significantly impaired cognition, higher levels of cognitive complaints, greater levels of tau and p-tau, and subcortical and cortical atrophy relative to HC participants (p < 0.05). Cortical amyloid deposition and CSF levels of Aβ were significantly associated with APOE ε4 status but not E-MCI diagnosis, with ε4 positive participants showing more amyloid deposition and lower levels of CSF Aβ than ε4 negative participants. Other effects of APOE ε4 status on cognition and CSF tau levels were also observed. Conclusions: APOE ε4 status is associated with amyloid accumulation and lower CSF Aβ, as well as increased CSF tau levels in early prodromal stages of AD (E-MCI) and HC. Alternatively, neurodegeneration, cognitive impairment, and increased complaints are primarily associated with a diagnosis of E-MCI. These findings underscore the importance of considering APOE genotype when evaluating biomarkers in early stages of disease.",
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AU - Risacher, Shannon L.

AU - Kim, Sungeun

AU - Shen, Li

AU - Nho, Kwangsik

AU - Foroud, Tatiana

AU - Green, Robert C.

AU - Petersen, Ronald C.

AU - Jack, Clifford R.

AU - Aisen, Paul S.

AU - Koeppe, Robert A.

AU - Jagust, William J.

AU - Shaw, Leslie M.

AU - Trojanowski, John Q.

AU - Weiner, Michael W.

AU - Saykin, Andrew

PY - 2013

Y1 - 2013

N2 - Objective: Our goal was to evaluate the association of APOE with amyloid deposition, cerebrospinal fluid levels (CSF) of Aβ, tau, and p-tau, brain atrophy, cognition and cognitive complaints in E-MCI patients and cognitively healthy older adults (HC) in the ADNI-2 cohort. Methods: Two-hundred and nine E-MCI and 123 HC participants from the ADNI-2 cohort were included. We evaluated the impact of diagnostic status (E-MCI vs. HC) and APOE ε4 status (ε4 positive vs. ε4 negative) on cortical amyloid deposition (AV-45/Florbetapir SUVR PET scans), brain atrophy (structural MRI scans processed using voxel-based morphometry and Freesurfer version 5.1), CSF levels of Aβ, tau, and p-tau, and cognitive performance and complaints. Results: E-MCI participants showed significantly impaired cognition, higher levels of cognitive complaints, greater levels of tau and p-tau, and subcortical and cortical atrophy relative to HC participants (p < 0.05). Cortical amyloid deposition and CSF levels of Aβ were significantly associated with APOE ε4 status but not E-MCI diagnosis, with ε4 positive participants showing more amyloid deposition and lower levels of CSF Aβ than ε4 negative participants. Other effects of APOE ε4 status on cognition and CSF tau levels were also observed. Conclusions: APOE ε4 status is associated with amyloid accumulation and lower CSF Aβ, as well as increased CSF tau levels in early prodromal stages of AD (E-MCI) and HC. Alternatively, neurodegeneration, cognitive impairment, and increased complaints are primarily associated with a diagnosis of E-MCI. These findings underscore the importance of considering APOE genotype when evaluating biomarkers in early stages of disease.

AB - Objective: Our goal was to evaluate the association of APOE with amyloid deposition, cerebrospinal fluid levels (CSF) of Aβ, tau, and p-tau, brain atrophy, cognition and cognitive complaints in E-MCI patients and cognitively healthy older adults (HC) in the ADNI-2 cohort. Methods: Two-hundred and nine E-MCI and 123 HC participants from the ADNI-2 cohort were included. We evaluated the impact of diagnostic status (E-MCI vs. HC) and APOE ε4 status (ε4 positive vs. ε4 negative) on cortical amyloid deposition (AV-45/Florbetapir SUVR PET scans), brain atrophy (structural MRI scans processed using voxel-based morphometry and Freesurfer version 5.1), CSF levels of Aβ, tau, and p-tau, and cognitive performance and complaints. Results: E-MCI participants showed significantly impaired cognition, higher levels of cognitive complaints, greater levels of tau and p-tau, and subcortical and cortical atrophy relative to HC participants (p < 0.05). Cortical amyloid deposition and CSF levels of Aβ were significantly associated with APOE ε4 status but not E-MCI diagnosis, with ε4 positive participants showing more amyloid deposition and lower levels of CSF Aβ than ε4 negative participants. Other effects of APOE ε4 status on cognition and CSF tau levels were also observed. Conclusions: APOE ε4 status is associated with amyloid accumulation and lower CSF Aβ, as well as increased CSF tau levels in early prodromal stages of AD (E-MCI) and HC. Alternatively, neurodegeneration, cognitive impairment, and increased complaints are primarily associated with a diagnosis of E-MCI. These findings underscore the importance of considering APOE genotype when evaluating biomarkers in early stages of disease.

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KW - Cerebrospinal fluid (CSF)

KW - Early mild cognitive impairment (E-MCI)

KW - Florbetapir/AV-45/Amyvid

KW - Magnetic resonance imaging (MRI)

KW - Positron emission tomography (PET)

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