April 28, 2009 | Nicola Filippini, Bradley J. MacIntosh, Morgan G. Hough, Guy M. Goodwin, Giovanni B. Frisoni, Stephen M. Smith, Paul M. Matthews, Christian F. Beckmann, and Clare E. Mackay
This study investigates the structural and functional brain differences in young healthy carriers of the APOE ε4 allele, a known risk factor for late-life pathological changes. The researchers used resting-state fMRI and an encoding memory paradigm to examine brain activity in 18 young APOE ε4-carriers and 18 matched noncarriers. Key findings include:
1. **Resting State fMRI**: APOE ε4-carriers showed increased coactivation in the default mode network (DMN), particularly in the retrosplenial, medial-prefrontal, and hippocampal regions, compared to noncarriers. This suggests that the ε4 allele may modulate brain function decades before any clinical or neurophysiological expression of neurodegenerative processes.
2. **Task-Related fMRI**: During a memory-encoding task, APOE ε4-carriers exhibited greater hippocampal activation compared to noncarriers. This activation was observed bilaterally in the hippocampus and cerebellum, with no differences in brain volume, resting perfusion, or memory performance between the two groups.
3. **Brain Morphology and Physiology**: No significant differences were found in whole-brain volume, GM volume, or resting perfusion between APOE ε4-carriers and noncarriers.
4. **Discussion**: The study demonstrates that the APOE ε4 allele influences brain function in young adults, particularly in the hippocampus and DMN, even before the onset of neurodegenerative processes. These findings suggest that the ε4 allele may play a fundamental role in brain function, potentially conferring systematic vulnerability in the memory system.
The study highlights the importance of further research to replicate these results in larger samples and to explore the long-term implications of these brain differences.This study investigates the structural and functional brain differences in young healthy carriers of the APOE ε4 allele, a known risk factor for late-life pathological changes. The researchers used resting-state fMRI and an encoding memory paradigm to examine brain activity in 18 young APOE ε4-carriers and 18 matched noncarriers. Key findings include:
1. **Resting State fMRI**: APOE ε4-carriers showed increased coactivation in the default mode network (DMN), particularly in the retrosplenial, medial-prefrontal, and hippocampal regions, compared to noncarriers. This suggests that the ε4 allele may modulate brain function decades before any clinical or neurophysiological expression of neurodegenerative processes.
2. **Task-Related fMRI**: During a memory-encoding task, APOE ε4-carriers exhibited greater hippocampal activation compared to noncarriers. This activation was observed bilaterally in the hippocampus and cerebellum, with no differences in brain volume, resting perfusion, or memory performance between the two groups.
3. **Brain Morphology and Physiology**: No significant differences were found in whole-brain volume, GM volume, or resting perfusion between APOE ε4-carriers and noncarriers.
4. **Discussion**: The study demonstrates that the APOE ε4 allele influences brain function in young adults, particularly in the hippocampus and DMN, even before the onset of neurodegenerative processes. These findings suggest that the ε4 allele may play a fundamental role in brain function, potentially conferring systematic vulnerability in the memory system.
The study highlights the importance of further research to replicate these results in larger samples and to explore the long-term implications of these brain differences.