Affiliations: [a] Premedical Science, College of Medicine, Chosun University, Gwangju, Korea
| [b] Department of Neuropsychiatry, School of Medicine, Chosun University/Chosun University Hospital, Gwangju, Korea
| [c] Department of Laboratory Medicine, School of Medicine, Chosun University/Chosun University Hospital, Gwangju, Korea
Correspondence:
[*]
Correspondence to: IL Han Choo, MD, PhD, Department of Neuropsychiatry, School of Medicine, Chosun University/Chosun University Hospital, 365 Pilmundaero Dong-gu Gwangju, 61452 South Korea. Tel.: +82 62 220 3104; Fax: +82 62 225 3659; E-mail: [email protected]
Note: [1] Data used in the preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). Therefore, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
Abstract: Background: APOE ɛ4 contributes to Alzheimer’s disease (AD) pathogenesis by amyloid-beta (Aβ)-dependent and Aβ-independent processes. Objective: We investigated the APOE ɛ4 influence on regional cerebral glucose metabolism (rCMglc) in the continuum of AD after Aβ adjustment. Methods: We included 318 cognitively normal (CN) elderly, 498 mild cognitive impairment (MCI), and 178 AD from the Alzheimer’s Disease Neuroimaging Initiative database. They had [18F] florbetapir positron emission tomography (PET) and [18F] fluorodeoxyglucose (FDG)-PET conducted within 3 months of a clinical and cognitive assessment visit and APOE genotype. At first, the rCMglc differences between APOE ɛ4 carriers (ɛ4+) and non-carriers (ɛ4–) were estimated on a voxel-based analysis using a ‘two-sample t-test’ design. In the second analysis, Aβ was added as covariate. Results: In CN, ɛ4+ showed reduced rCMglc compared to ɛ4–in the bilateral frontal, temporal, and the left parietal regions. In MCI, ɛ4+ showed reduced rCMglc compared to ɛ4– in the bilateral posterior parietal, temporal, and left frontal regions. In AD, ɛ4+ showed reduced rCMglc in the left hippocampus, right insular, and right temporal gyrus. However, after Aβ adjustment, the significant differences in the temporal regions were absent in CN and MCI, and none of the areas detected as significant in the first analysis were statistically significant in AD. Conclusions: Our study demonstrated that Aβ-independent APOE ɛ4 influence on rCMglc is limited to the parietal and frontal, but not temporal lobes. These results suggest that APOE ɛ4 may predispose for regional vulnerability according to Aβ-independent and Aβ-dependent processes.
