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, Laurel A Beckett, Paul S. Aisen, Robert A. Koeppe, William J. Jagust, Leslie M. Shaw, John Q. Trojanowski, Michael W. Weiner, Andrew J. Saykin, Disease Neuroimaging Initiative (ADNI) Alzheimer's Disease Neuroimaging Initiative (ADNI)

Research output: Contribution to journalArticle

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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 [18F]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.

Original languageEnglish (US)
Pages (from-to)1417-1429
Number of pages13
JournalAlzheimer's and Dementia
Volume11
Issue number12
DOIs
StatePublished - Dec 1 2015

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Apolipoproteins E
Alzheimer Disease
Biomarkers
Apolipoprotein E4
Amyloid
Temporal Lobe
Cerebrospinal Fluid
Neuroimaging
Atrophy

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Epidemiology
  • Health Policy

Cite this

Risacher, S. L., Kim, S., Nho, K., Foroud, T., Shen, L., Petersen, R. C., ... Alzheimer's Disease Neuroimaging Initiative (ADNI), D. N. I. ADNI. (2015). APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern. Alzheimer's and Dementia, 11(12), 1417-1429. https://doi.org/10.1016/j.jalz.2015.03.003

APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern. / 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.; Alzheimer's Disease Neuroimaging Initiative (ADNI), Disease Neuroimaging Initiative (ADNI).

In: Alzheimer's and Dementia, Vol. 11, No. 12, 01.12.2015, p. 1417-1429.

Research output: Contribution to journalArticle

Risacher, SL, Kim, S, Nho, K, Foroud, T, Shen, L, Petersen, RC, Jack, CR, Beckett, LA, Aisen, PS, Koeppe, RA, Jagust, WJ, Shaw, LM, Trojanowski, JQ, Weiner, MW, Saykin, AJ & Alzheimer's Disease Neuroimaging Initiative (ADNI), DNIADNI 2015, 'APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern', Alzheimer's and Dementia, vol. 11, no. 12, pp. 1417-1429. 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. ; Saykin, Andrew J. ; Alzheimer's Disease Neuroimaging Initiative (ADNI), Disease Neuroimaging Initiative (ADNI). / APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern. In: Alzheimer's and Dementia. 2015 ; Vol. 11, No. 12. pp. 1417-1429.
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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 [18F]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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T1 - APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern

AU - Risacher, Shannon L.

AU - Kim, Sungeun

AU - Nho, Kwangsik

AU - Foroud, Tatiana

AU - Shen, Li

AU - Petersen, Ronald C.

AU - Jack, Clifford R.

AU - Beckett, Laurel A

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.

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N2 - 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 [18F]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.

AB - 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 [18F]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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