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Time Course of Glucose Metabolism in Relation to Cognitive Performance and Postmortem Neuropathology in Met146Val PSEN1 Mutation Carriers
Uppsala Imanet AB, GE Healthcare, Uppsala, Sweden.
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2011 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, Vol. 24, no 3, 495-506 p.Article in journal (Refereed) Published
Abstract [en]

Studies in carriers of mutations that cause early-onset familial Alzheimer's disease (eoFAD) are of significant interest. We showed previously that regional glucose hypometabolism could be detected many years before disease onset in presenilin 1 (PSEN1) mutation carriers. Here we studied four members of a family with a Met146Val PSEN1 mutation, two symptomatic carriers and two non-carriers, longitudinally with 18F-FDG PET over a period of about two and four years, respectively. The two mutation carriers showed global cortical glucose hypometabolism over time with the most distinct decline occurring in the posterior cingulate, the parietal and parietotemporal cortex, which was also observed when compared with a group of 23 healthy controls and a group 27 sporadic Alzheimer's disease (sAD) patients. This decline correlated with cognitive deterioration over time as measured by neuropsychological tests. Postmortem examination of brain tissue revealed substantially elevated levels of AD type neuropathology in terms of neuritic plaques and neurofibrillary tangles in the two mutation carriers compared with a reference group of sAD patients. In the mutation carriers, the amount of neuritic plaques but not neurofibrillary tangles correlated hereby significantly with regional glucose metabolism as measured by 18F-FDG on the last scanning occasions, which were performed four and approximately five years before death, respectively. We here show that FDG PET can depict in vivo the aggressive disease progression in eoFAD mutation carriers in relationship to neuropathology.

Place, publisher, year, edition, pages
2011. Vol. 24, no 3, 495-506 p.
Keyword [en]
Early-onset familial Alzheimer's disease, FDG, longitudinal studies, neuritic plaques, neurofibrillary tangles, postitron emission tomography, postmortem pathology, presenilin 1
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URN: urn:nbn:se:uu:diva-156688DOI: 10.3233/JAD-2011-101563ISI: 000292496900007OAI: oai:DiVA.org:uu-156688DiVA: diva2:432862
Available from: 2011-08-08 Created: 2011-08-07 Last updated: 2014-06-05Bibliographically approved

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Wall, AndersLångström, Bengt
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Department of Biochemistry and Organic Chemistry
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