Journal Article

Reduced functional brain activity response in cognitively intact <i>apolipoprotein E</i> ε4 carriers

Johanna Lind, Jonas Persson, Martin Ingvar, Anne Larsson, Marc Cruts, Christine Van Broeckhoven, Rolf Adolfsson, Lars Bäckman, Lars-Göran Nilsson, Karl Magnus Petersson and Lars Nyberg

in Brain

Published on behalf of The Guarantors of Brain

Volume 129, issue 5, pages 1240-1248
Published in print May 2006 | ISSN: 0006-8950
Published online March 2006 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awl054
Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers

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The apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE ε4 carriers (age range: 49–74 years; 19 females), of which 10 were homozygous for the ε4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE ε4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE ε4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.

Keywords: Alzheimer's disease; apolipoprotein E; memory; fMRI; APOE = apolipoprotein E; BA = Brodmann area; fMRI = functional MRI; MTL = medial temporal lobe; SPMs = statistical parametric maps

Journal Article.  6579 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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