Greater medial temporal hypometabolism and lower cortical amyloid burden in ApoE4-positive AD patients
Manja Lehmann1, Pia M Ghosh, Cindee Madison
1Department of Neurology, Memory & Aging Center, University of California, , San Francisco, California, USA.
Background:
Apolipoprotein E ε4 (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 [(11)C]Pittsburgh compound B (PIB) and [(18)F]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.
Insights
The presence of Apolipoprotein E ε4 (ApoE4) in Alzheimer's disease (AD) patients correlates with lower amyloid deposition but increased medial temporal hypometabolism. This suggests ApoE4 influences AD pathology and neurodegeneration patterns.
Area of Science:
- Neuroscience
- Genetics
- Radiology
Background:
- Apolipoprotein E ε4 (ApoE4) is linked to increased Alzheimer's disease (AD) risk, amyloid deposition, and hypometabolism.
- ApoE4's prevalence in non-amnestic AD variants suggests a role in clinical phenotype, but its impact on amyloid and metabolism across AD syndromes is unclear.
Purpose of the Study:
- To investigate the relationship between amyloid deposition, glucose metabolism, and ApoE4 genotype in a diverse group of AD patients.
Main Methods:
- 52 probable AD patients underwent [(11)C]Pittsburgh compound B (PIB) and [(18)F]fluorodeoxyglucose (FDG) PET scans.
- Patients were categorized as ApoE4 positive (ApoE4+) or negative (ApoE4-), including language-variant, visual-variant, and amnestic/dysexecutive AD subtypes.
- FDG and PIB uptake were compared voxel-wise and in regions of interest against 52 healthy controls.
Main Results:
- ApoE4- patients exhibited higher cortical PIB uptake, particularly in right lateral frontotemporal regions, compared to ApoE4+ patients.
- Both patient groups showed similar hypometabolism patterns (temporoparietal, precuneus, cingulate, frontal cortex) relative to controls.
- ApoE4+ patients displayed greater medial temporal hypometabolism, while ApoE4- patients showed more cortical hypometabolism in specific frontal areas.
Conclusions:
- ApoE4+ AD patients present with reduced global amyloid burden and heightened medial temporal hypometabolism compared to ApoE4- patients.
- These findings indicate that ApoE4 may enhance susceptibility to molecular pathology and modify the anatomical distribution of neurodegeneration in AD.
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