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

Authors


  • Data used in the preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu\ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data, but did not participate in analysis or the writing of this report. A complete listing of ADNI investigators is available at www.loni.ucla.edu\ADNI\Collaboration\ADNI_Manuscript_Citations.pdf

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 Aβ1–42 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. ANN NEUROL 2010;67:308–316

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