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          Institute: MPI für Psycholinguistik     Collection: The Neurobiology of Language     Display Documents

ID: 322767.0, MPI für Psycholinguistik / The Neurobiology of Language
Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers
Authors:Lind, Johanna; Persson, Jonas; Ingvar, Martin; Larsson, Anne; Cruts, Marc; Van Broeckhoven, Christine; Adolfsson, Rolf; Bäckman, Lars; Nilsson, Lars-Göran; Petersson, Karl Magnus; Nyberg, Lars
Date of Publication (YYYY-MM-DD):2006
Title of Journal:Brain
Issue / Number:5
Start Page:1240
End Page:1248
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) 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 {varepsilon}4 carriers (age range: 49–74 years; 19 females), of which 10 were homozygous for the {varepsilon}4 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 {varepsilon}4 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 {varepsilon}4 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.
External Publication Status:published
Document Type:Article
Communicated by:Peter Hagoort
Affiliations:MPI für Psycholinguistik
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