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APOE-epsilon4 is associated with less frontal and more medial temporal lobe atrophy in AD
C Geroldi1, M Pihlajamäki, M P Laakso
1IRCCS San Giovanni di Dio-FBF, Brescia, Italy.
Objective:
To test the hypothesis that the e4 allele of APOE is associated with a region-specific pattern of brain atrophy in AD.
Methods:
Volumes of the hippocampi, entorhinal cortices, and anterior temporal and frontal lobes were measured in 28 mild to moderate AD patients and 30 controls using MRI. Within the AD group, 14 patients were noncarriers (-/-), 9 were heterozygous (e4/-), and 5 were homozygous (e4/4) for the e4 allele. Dementia severity was similar across the three AD groups.
Results:
Smaller volumes were found with increasing dose of the e4 allele in the hippocampus, entorhinal cortex, and anterior temporal lobes in AD patients. When compared with controls, the volume loss in the right and left temporal regions ranged from -15.3 to -22.7% in the -/- AD group, from -26.2 to -36.0% in the e4/- group, and from -24.0 to -48.0% in the e4/4 group (p < 0.0005). In contrast, larger volumes were found in the frontal lobes with increasing e4 gene dose. When compared with controls, volume differences of the right frontal lobe were -11.8% in the -/- AD group, -8.5 in the e4/- group, and -1.4% in the e4/4 group (p = 0.03).
Conclusions:
We found smaller volumes in the temporal lobe regions but larger volumes in the frontal lobes with increasing APOE-e4 gene dose in AD patients. These data suggest a region-specific biological effect of the e4 allele in the brains of AD patients.
Insights
The APOE-e4 allele is linked to brain atrophy in specific regions of Alzheimer's disease (AD) patients. Increasing doses of the e4 allele correlate with smaller temporal lobe volumes and larger frontal lobe volumes in AD.
Area of Science:
- Neuroscience
- Genetics
- Radiology
Background:
- Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline.
- The apolipoprotein E (APOE) gene, particularly the e4 allele, is a significant genetic risk factor for late-onset AD.
- The specific pattern of brain atrophy associated with APOE-e4 in AD remains an area of active investigation.
Purpose of the Study:
- To investigate the association between the APOE e4 allele and region-specific brain atrophy in patients with Alzheimer's disease.
- To determine if the dose of the APOE e4 allele influences the extent and pattern of brain volume loss.
Main Methods:
- Magnetic Resonance Imaging (MRI) was used to measure brain volumes in AD patients and controls.
- Specific brain regions analyzed included hippocampi, entorhinal cortices, and anterior temporal and frontal lobes.
- AD patients were categorized based on their APOE e4 allele status: noncarriers (-/-), heterozygous (e4/-), and homozygous (e4/4).
Main Results:
- A dose-dependent relationship was observed between the APOE e4 allele and reduced volumes in the hippocampus, entorhinal cortex, and anterior temporal lobes in AD patients.
- AD patients with increasing APOE e4 allele dose showed significantly greater volume loss in temporal regions compared to controls.
- Conversely, larger volumes were observed in the frontal lobes with increasing APOE e4 gene dose in AD patients.
Conclusions:
- The APOE e4 allele is associated with region-specific patterns of brain atrophy in Alzheimer's disease.
- Temporal lobe regions exhibit atrophy, while frontal lobes show volume expansion in relation to APOE e4 gene dose in AD.
- These findings suggest a distinct biological mechanism of the APOE e4 allele affecting brain structure in AD patients.