Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers.
2006 (English)In: Brain: A Journal of Neurology, ISSN 0006-8950, Vol. 129, no 5, 1240-1248 p.Article in journal (Refereed) Published
The Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer’s disease (AD). Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis of AD. We have conducted a large-scale fMRI study, where we contrasted 30 APOE ε4 carriers and 30 non-carriers with regard to brain activity during a semantic categorization task. Critically, both groups were cognitively intact and AD-symptom free. APOE ε4 carriers showed redued 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 to heterozygous carriers. In addition, contrasts of processing novel vs. 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 AD, well before alterations can be detected at the behavioral level.
Place, publisher, year, edition, pages
2006. Vol. 129, no 5, 1240-1248 p.
apolipoprotein E, Alzheimers disease, brain activity, semantic categorization, memory, genetics, brain imaging
IdentifiersURN: urn:nbn:se:su:diva-19436DOI: doi:10.1093/brain/awl054OAI: oai:DiVA.org:su-19436DiVA: diva2:185960
This work was supported by grants from the Bank of Sweden Tercentenary Foundation (J2001-0683:3), the Swedish Research Council (2003-5810) and Fund for Scientific Research Flanders (FWO). The Betula Study from where subjects were recruited is funded by the Bank of Sweden Tercentenary Foundation (1988-0082:17, J2001-0682), Swedish Council for Planning and Coordination of Research (D1988-0092, D1989-0115, D1990-0074, D1991-0258, D1992-0143, D1997-0756, D1997-1841, D1999-0739, B1999-474), Swedish Council for Research in the Humanities and Social Sciences (F377/1988-2000), the Swedish Councilfor Social Research (1988-1990: 88-0082, and 311/1991-2000) and the Swedish Research Council (2001-6654, 2002-3794, 2003-3883).2007-11-122007-11-122011-01-11Bibliographically approved