Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease

Prashanthi D Vemuri, Heather J. Wiste, Stephen D. Weigand, David S Knopman, Leslie M. Shaw, John Q. Trojanowski, Paul S. Aisen, Michael Weiner, Ronald Carl Petersen, Clifford R Jr. Jack

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Objective: To study the effect of apolipoprotein E ε4 status on biomarkers of neurodegeneration (atrophy on magnetic resonance imaging [MRI]), neuronal injury (cerebrospinal fluid [CSF] t-tau), and brain Aβ amyloid load (CSF Aβ1-42) in cognitively normal subjects (CN), amnestic subjects with mild cognitive impairment (aMCI), and patients with Alzheimer disease (AD). Methods: We included all 399 subjects (109 CN, 192 aMCI, 98 AD) from the Alzheimer's Disease Neuroimaging Initiative study with baseline CSF and MRI scans. Structural Abnormality Index (STAND) scores, which reflect the degree of AD-like anatomic features on MRI, were computed for each subject. Results: A clear ε4 allele dose effect was seen on CSF Aβ 1-42 levels within each clinical group. In addition, the proportion of the variability in Aβ1-42 levels explained by APOE ε4 dose was significantly greater than the proportion of the variability explained by clinical diagnosis. On the other hand, the proportion of the variability in CSF t-tau and MRI atrophy explained by clinical diagnosis was greater than the proportion of the variability explained by APOE ε4 dose; however, this effect was only significant for STAND scores. Interpretation: Low CSF Aβ1-42 (surrogate for Aβ amyloid load) is more closely linked to the presence of APOE ε4 than to clinical status. In contrast, MRI atrophy (surrogate for neurodegeneration) is closely linked with cognitive impairment, whereas its association with APOE ε4 is weaker. The data in this paper support a model of AD in which CSF Aβ1-42 is the earliest of the 3 biomarkers examined to become abnormal in both APOE carriers and noncarriers.

Original languageEnglish (US)
Pages (from-to)308-316
Number of pages9
JournalAnnals of Neurology
Volume67
Issue number3
DOIs
StatePublished - Mar 2010

Fingerprint

Apolipoproteins E
Amyloid
Cerebrospinal Fluid
Alzheimer Disease
Biomarkers
Pathology
Magnetic Resonance Imaging
Atrophy
Apolipoprotein E4
Neuroimaging
Alleles
Wounds and Injuries
Brain
Cognitive Dysfunction

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease. / Vemuri, Prashanthi D; Wiste, Heather J.; Weigand, Stephen D.; Knopman, David S; Shaw, Leslie M.; Trojanowski, John Q.; Aisen, Paul S.; Weiner, Michael; Petersen, Ronald Carl; Jack, Clifford R Jr.

In: Annals of Neurology, Vol. 67, No. 3, 03.2010, p. 308-316.

Research output: Contribution to journalArticle

Vemuri, Prashanthi D ; Wiste, Heather J. ; Weigand, Stephen D. ; Knopman, David S ; Shaw, Leslie M. ; Trojanowski, John Q. ; Aisen, Paul S. ; Weiner, Michael ; Petersen, Ronald Carl ; Jack, Clifford R Jr. / Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease. In: Annals of Neurology. 2010 ; Vol. 67, No. 3. pp. 308-316.
@article{af98f0bd69b24fb0a277c63acb79feae,
title = "Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease",
abstract = "Objective: To study the effect of apolipoprotein E ε4 status on biomarkers of neurodegeneration (atrophy on magnetic resonance imaging [MRI]), neuronal injury (cerebrospinal fluid [CSF] t-tau), and brain Aβ amyloid load (CSF Aβ1-42) in cognitively normal subjects (CN), amnestic subjects with mild cognitive impairment (aMCI), and patients with Alzheimer disease (AD). Methods: We included all 399 subjects (109 CN, 192 aMCI, 98 AD) from the Alzheimer's Disease Neuroimaging Initiative study with baseline CSF and MRI scans. Structural Abnormality Index (STAND) scores, which reflect the degree of AD-like anatomic features on MRI, were computed for each subject. Results: A clear ε4 allele dose effect was seen on CSF Aβ 1-42 levels within each clinical group. In addition, the proportion of the variability in Aβ1-42 levels explained by APOE ε4 dose was significantly greater than the proportion of the variability explained by clinical diagnosis. On the other hand, the proportion of the variability in CSF t-tau and MRI atrophy explained by clinical diagnosis was greater than the proportion of the variability explained by APOE ε4 dose; however, this effect was only significant for STAND scores. Interpretation: Low CSF Aβ1-42 (surrogate for Aβ amyloid load) is more closely linked to the presence of APOE ε4 than to clinical status. In contrast, MRI atrophy (surrogate for neurodegeneration) is closely linked with cognitive impairment, whereas its association with APOE ε4 is weaker. The data in this paper support a model of AD in which CSF Aβ1-42 is the earliest of the 3 biomarkers examined to become abnormal in both APOE carriers and noncarriers.",
author = "Vemuri, {Prashanthi D} and Wiste, {Heather J.} and Weigand, {Stephen D.} and Knopman, {David S} and Shaw, {Leslie M.} and Trojanowski, {John Q.} and Aisen, {Paul S.} and Michael Weiner and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.}",
year = "2010",
month = "3",
doi = "10.1002/ana.21953",
language = "English (US)",
volume = "67",
pages = "308--316",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease

AU - Vemuri, Prashanthi D

AU - Wiste, Heather J.

AU - Weigand, Stephen D.

AU - Knopman, David S

AU - Shaw, Leslie M.

AU - Trojanowski, John Q.

AU - Aisen, Paul S.

AU - Weiner, Michael

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

PY - 2010/3

Y1 - 2010/3

N2 - Objective: To study the effect of apolipoprotein E ε4 status on biomarkers of neurodegeneration (atrophy on magnetic resonance imaging [MRI]), neuronal injury (cerebrospinal fluid [CSF] t-tau), and brain Aβ amyloid load (CSF Aβ1-42) in cognitively normal subjects (CN), amnestic subjects with mild cognitive impairment (aMCI), and patients with Alzheimer disease (AD). Methods: We included all 399 subjects (109 CN, 192 aMCI, 98 AD) from the Alzheimer's Disease Neuroimaging Initiative study with baseline CSF and MRI scans. Structural Abnormality Index (STAND) scores, which reflect the degree of AD-like anatomic features on MRI, were computed for each subject. Results: A clear ε4 allele dose effect was seen on CSF Aβ 1-42 levels within each clinical group. In addition, the proportion of the variability in Aβ1-42 levels explained by APOE ε4 dose was significantly greater than the proportion of the variability explained by clinical diagnosis. On the other hand, the proportion of the variability in CSF t-tau and MRI atrophy explained by clinical diagnosis was greater than the proportion of the variability explained by APOE ε4 dose; however, this effect was only significant for STAND scores. Interpretation: Low CSF Aβ1-42 (surrogate for Aβ amyloid load) is more closely linked to the presence of APOE ε4 than to clinical status. In contrast, MRI atrophy (surrogate for neurodegeneration) is closely linked with cognitive impairment, whereas its association with APOE ε4 is weaker. The data in this paper support a model of AD in which CSF Aβ1-42 is the earliest of the 3 biomarkers examined to become abnormal in both APOE carriers and noncarriers.

AB - Objective: To study the effect of apolipoprotein E ε4 status on biomarkers of neurodegeneration (atrophy on magnetic resonance imaging [MRI]), neuronal injury (cerebrospinal fluid [CSF] t-tau), and brain Aβ amyloid load (CSF Aβ1-42) in cognitively normal subjects (CN), amnestic subjects with mild cognitive impairment (aMCI), and patients with Alzheimer disease (AD). Methods: We included all 399 subjects (109 CN, 192 aMCI, 98 AD) from the Alzheimer's Disease Neuroimaging Initiative study with baseline CSF and MRI scans. Structural Abnormality Index (STAND) scores, which reflect the degree of AD-like anatomic features on MRI, were computed for each subject. Results: A clear ε4 allele dose effect was seen on CSF Aβ 1-42 levels within each clinical group. In addition, the proportion of the variability in Aβ1-42 levels explained by APOE ε4 dose was significantly greater than the proportion of the variability explained by clinical diagnosis. On the other hand, the proportion of the variability in CSF t-tau and MRI atrophy explained by clinical diagnosis was greater than the proportion of the variability explained by APOE ε4 dose; however, this effect was only significant for STAND scores. Interpretation: Low CSF Aβ1-42 (surrogate for Aβ amyloid load) is more closely linked to the presence of APOE ε4 than to clinical status. In contrast, MRI atrophy (surrogate for neurodegeneration) is closely linked with cognitive impairment, whereas its association with APOE ε4 is weaker. The data in this paper support a model of AD in which CSF Aβ1-42 is the earliest of the 3 biomarkers examined to become abnormal in both APOE carriers and noncarriers.

UR - http://www.scopus.com/inward/record.url?scp=77950545456&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950545456&partnerID=8YFLogxK

U2 - 10.1002/ana.21953

DO - 10.1002/ana.21953

M3 - Article

VL - 67

SP - 308

EP - 316

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 3

ER -