Greater medial temporal hypometabolism and lower cortical amyloid burden in ApoE4-positive AD patients
- Manja Lehmann1,2,3,
- Pia M Ghosh1,2,
- Cindee Madison2,
- Anna Karydas1,
- Giovanni Coppola4,
- James P O'Neil5,
- Yadong Huang6,
- Bruce L Miller1,
- William J Jagust1,2,5,
- Gil D Rabinovici1,2,5
- 1Department of Neurology, Memory & Aging Center, University of California, San Francisco, California, USA
- 2Helen Wills Neuroscience Institute, University of California, Berkeley, California, USA
- 3Dementia Research Centre, University College London, National Hospital for Neurology and Neurosurgery, London, UK
- 4Departments of Psychiatry and Neurology, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- 5Lawrence Berkeley National Laboratory, Berkeley, California, USA
- 6Departments of Neurology and Pathology, Gladstone Institute of Neurological Disease, University of California, San Francisco, California, USA
- Correspondence to Dr Manja Lehmann, Dementia Research Centre, University College London, National Hospital for Neurology and Neurosurgery, Box 16, London WC1N 3BG, UK;
- Received 15 May 2013
- Revised 23 July 2013
- Accepted 4 August 2013
- Published Online First 21 August 2013
Background Apolipoprotein E ɛ4 (ApoE4) has been associated with an increased risk of Alzheimer's disease (AD), amyloid deposition and hypometabolism. ApoE4 is less prevalent in non-amnestic AD variants suggesting a direct effect on the clinical phenotype. However, the impact of ApoE4 on amyloid burden and glucose metabolism across different clinical AD syndromes is not well understood. We aimed to assess the relationship between amyloid deposition, glucose metabolism and ApoE4 genotype in a clinically heterogeneous population of AD patients.
Methods 52 patients with probable AD (National Institute on Aging-Alzheimer's Association) underwent [11C]Pittsburgh compound B (PIB) and [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. All patients had positive PIB-PET scans. 23 were ApoE4 positive (ApoE4+) (14 heterozygous and 9 homozygous) and 29 were ApoE4 negative (ApoE4−). Groups consisted of language-variant AD, visual-variant AD and AD patients with amnestic and dysexecutive deficits. 52 healthy controls were included for comparison. FDG and PIB uptake was compared between groups on a voxel-wise basis and in regions of interest.
Results While PIB patterns were diffuse in both patient groups, ApoE4− patients showed higher PIB uptake than ApoE4+ patients across the cortex. Higher PIB uptake in ApoE4− patients was particularly significant in right lateral frontotemporal regions. In contrast, similar patterns of hypometabolism relative to controls were found in both patient groups, mainly involving lateral temporoparietal cortex, precuneus, posterior cingulate cortex and middle frontal gyrus. Comparing patient groups, ApoE4+ subjects showed greater hypometabolism in bilateral medial temporal and right lateral temporal regions, and ApoE4− patients showed greater hypometabolism in cortical areas, including supplementary motor cortex and superior frontal gyrus.
Conclusions ApoE4+ AD patients showed lower global amyloid burden and greater medial temporal hypometabolism compared with matched ApoE4− patients. These findings suggest that ApoE4 may increase susceptibility to molecular pathology and modulate the anatomic pattern of neurodegeneration in AD.