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Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease.
Ann Neurol 2010; 67(3):308-16AN

Abstract

OBJECTIVE

To study the effect of apolipoprotein E epsilon4 status on biomarkers of neurodegeneration (atrophy on magnetic resonance imaging [MRI]), neuronal injury (cerebrospinal fluid [CSF] t-tau), and brain Abeta amyloid load (CSF Abeta(1-42)) 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 epsilon4 allele dose effect was seen on CSF Abeta(1-42) levels within each clinical group. In addition, the proportion of the variability in Abeta(1-42) levels explained by APOE epsilon4 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 epsilon4 dose; however, this effect was only significant for STAND scores.

INTERPRETATION

Low CSF Abeta(1-42) (surrogate for Abeta amyloid load) is more closely linked to the presence of APOE epsilon4 than to clinical status. In contrast, MRI atrophy (surrogate for neurodegeneration) is closely linked with cognitive impairment, whereas its association with APOE epsilon4 is weaker. The data in this paper support a model of AD in which CSF Abeta(1-42) is the earliest of the 3 biomarkers examined to become abnormal in both APOE carriers and noncarriers.

Authors+Show Affiliations

Aging and Dementia Imaging Research Laboratory, Department of Radiology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20373342

Citation

Vemuri, Prashanthi, et al. "Effect of Apolipoprotein E On Biomarkers of Amyloid Load and Neuronal Pathology in Alzheimer Disease." Annals of Neurology, vol. 67, no. 3, 2010, pp. 308-16.
Vemuri P, Wiste HJ, Weigand SD, et al. Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease. Ann Neurol. 2010;67(3):308-16.
Vemuri, P., Wiste, H. J., Weigand, S. D., Knopman, D. S., Shaw, L. M., Trojanowski, J. Q., ... Jack, C. R. (2010). Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease. Annals of Neurology, 67(3), pp. 308-16. doi:10.1002/ana.21953.
Vemuri P, et al. Effect of Apolipoprotein E On Biomarkers of Amyloid Load and Neuronal Pathology in Alzheimer Disease. Ann Neurol. 2010;67(3):308-16. PubMed PMID: 20373342.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of apolipoprotein E on biomarkers of amyloid load and neuronal pathology in Alzheimer disease. AU - Vemuri,Prashanthi, 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 C, AU - Jack,Clifford R,Jr AU - ,, PY - 2010/4/8/entrez PY - 2010/4/8/pubmed PY - 2010/6/9/medline SP - 308 EP - 16 JF - Annals of neurology JO - Ann. Neurol. VL - 67 IS - 3 N2 - OBJECTIVE: To study the effect of apolipoprotein E epsilon4 status on biomarkers of neurodegeneration (atrophy on magnetic resonance imaging [MRI]), neuronal injury (cerebrospinal fluid [CSF] t-tau), and brain Abeta amyloid load (CSF Abeta(1-42)) 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 epsilon4 allele dose effect was seen on CSF Abeta(1-42) levels within each clinical group. In addition, the proportion of the variability in Abeta(1-42) levels explained by APOE epsilon4 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 epsilon4 dose; however, this effect was only significant for STAND scores. INTERPRETATION: Low CSF Abeta(1-42) (surrogate for Abeta amyloid load) is more closely linked to the presence of APOE epsilon4 than to clinical status. In contrast, MRI atrophy (surrogate for neurodegeneration) is closely linked with cognitive impairment, whereas its association with APOE epsilon4 is weaker. The data in this paper support a model of AD in which CSF Abeta(1-42) is the earliest of the 3 biomarkers examined to become abnormal in both APOE carriers and noncarriers. SN - 1531-8249 UR - https://www.unboundmedicine.com/medline/citation/20373342/Effect_of_apolipoprotein_E_on_biomarkers_of_amyloid_load_and_neuronal_pathology_in_Alzheimer_disease_ L2 - https://doi.org/10.1002/ana.21953 DB - PRIME DP - Unbound Medicine ER -