TY - JOUR
T1 - The role of apolipoprotein E (APOE) genotype in early mild cognitive impairment (E-MCI)
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 J.
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.
KW - Alzheimer's disease neuroimaging initiative (ADNI)
KW - Apolipoprotein E (APOE)
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)
UR - http://www.scopus.com/inward/record.url?scp=84883268559&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883268559&partnerID=8YFLogxK
U2 - 10.3389/fnagi.2013.00011
DO - 10.3389/fnagi.2013.00011
M3 - Article
C2 - 23554593
AN - SCOPUS:84883268559
SN - 1663-4365
VL - 5
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
IS - APR
M1 - Article 11
ER -