Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers
Identifieur interne : 001620 ( Main/Exploration ); précédent : 001619; suivant : 001621Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers
Auteurs : Johanna Lind ; Jonas Persson ; Martin Ingvar ; Anne Larsson ; Marc Cruts [Belgique] ; Christine Van Broeckhoven [Belgique] ; Rolf Adolfsson ; Lars Ba Ckman ; Lars-Go Ran Nilsson ; Karl Magnus Petersson ; Lars NybergSource :
- Brain [ 0006-8950 ] ; 2006-05.
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- KwdEn :
Abstract
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.
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DOI: 10.1093/brain/awl054
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d'Anvers</region></placeName></affiliation><affiliation></affiliation></author><author><name sortKey="Adolfsson, Rolf" sort="Adolfsson, Rolf" uniqKey="Adolfsson R" first="Rolf" last="Adolfsson">Rolf Adolfsson</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Ba Ckman, Lars" sort="Ba Ckman, Lars" uniqKey="Ba Ckman L" first="Lars" last="Ba Ckman">Lars Ba Ckman</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Nilsson, Lars Go Ran" sort="Nilsson, Lars Go Ran" uniqKey="Nilsson L" first="Lars-Go Ran" last="Nilsson">Lars-Go Ran Nilsson</name><affiliation></affiliation><affiliation><wicri:noCountry code="subField"></wicri:noCountry></affiliation></author><author><name sortKey="Petersson, Karl Magnus" sort="Petersson, Karl Magnus" uniqKey="Petersson K" first="Karl Magnus" last="Petersson">Karl Magnus 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type="local">awl054</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>APOE = apolipoprotein E</term><term>Alzheimer's disease</term><term>BA = Brodmann area</term><term>MTL = medial temporal lobe</term><term>SPMs = statistical parametric maps</term><term>apolipoprotein E</term><term>fMRI</term><term>fMRI = functional MRI</term><term>memory</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Belgique</li></country><region><li>Province d'Anvers</li></region><settlement><li>Anvers</li></settlement><orgName><li>Université d'Anvers</li></orgName></list><tree><noCountry><name sortKey="Adolfsson, Rolf" sort="Adolfsson, Rolf" uniqKey="Adolfsson R" first="Rolf" last="Adolfsson">Rolf Adolfsson</name><name sortKey="Ba Ckman, Lars" sort="Ba Ckman, Lars" uniqKey="Ba Ckman L" first="Lars" last="Ba Ckman">Lars Ba Ckman</name><name sortKey="Ingvar, Martin" sort="Ingvar, Martin" uniqKey="Ingvar M" first="Martin" last="Ingvar">Martin Ingvar</name><name sortKey="Larsson, Anne" sort="Larsson, Anne" uniqKey="Larsson A" first="Anne" last="Larsson">Anne Larsson</name><name sortKey="Lind, Johanna" sort="Lind, Johanna" uniqKey="Lind J" first="Johanna" last="Lind">Johanna Lind</name><name sortKey="Nilsson, Lars Go Ran" sort="Nilsson, Lars Go Ran" uniqKey="Nilsson L" first="Lars-Go Ran" last="Nilsson">Lars-Go Ran Nilsson</name><name sortKey="Nyberg, Lars" sort="Nyberg, Lars" uniqKey="Nyberg L" first="Lars" last="Nyberg">Lars Nyberg</name><name sortKey="Persson, Jonas" sort="Persson, Jonas" uniqKey="Persson J" first="Jonas" last="Persson">Jonas Persson</name><name sortKey="Petersson, Karl Magnus" sort="Petersson, Karl Magnus" uniqKey="Petersson K" first="Karl Magnus" last="Petersson">Karl Magnus Petersson</name></noCountry><country name="Belgique"><region name="Province d'Anvers"><name sortKey="Cruts, Marc" sort="Cruts, Marc" uniqKey="Cruts M" first="Marc" last="Cruts">Marc Cruts</name></region><name sortKey="Van Broeckhoven, Christine" sort="Van Broeckhoven, Christine" uniqKey="Van Broeckhoven C" first="Christine" last="Van Broeckhoven">Christine Van Broeckhoven</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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