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Early astrocytosis in autosomal dominant Alzheimer's disease measured in vivo by multi-tracer positron emission tomography
Karolinska Inst, Ctr Alzheimer Res, Dept NVS, Div Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden.;Univ Gothenburg, MedTech West, S-41345 Gothenburg, Sweden.;Univ Gothenburg, Dept Clin Neurosci & Rehabil, S-41345 Gothenburg, Sweden..
Karolinska Inst, Ctr Alzheimer Res, Dept NVS, Div Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden.;Univ Manchester, Wolfson Mol Imaging Ctr, Manchester M20 3LJ, Lancs, England..
Karolinska Inst, Ctr Alzheimer Res, Dept NVS, Div Clin Geriatr, S-14157 Huddinge, Sweden..
Karolinska Inst, Ctr Alzheimer Res, Dept NVS, Div Translat Alzheimer Neurobiol, S-14157 Huddinge, Sweden..
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2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 16404Article in journal (Refereed) Published
Abstract [en]

Studying autosomal dominant Alzheimer's disease (ADAD), caused by gene mutations yielding nearly complete penetrance and a distinct age of symptom onset, allows investigation of presymptomatic pathological processes that can identify a therapeutic window for disease-modifying therapies. Astrocyte activation may occur in presymptomatic Alzheimer's disease (AD) because reactive astrocytes surround beta-amyloid (A beta) plaques in autopsy brain tissue. Positron emission tomography was performed to investigate fibrillar A beta, astrocytosis and cerebral glucose metabolism with the radiotracers C-11-Pittsburgh compound-B (PIB), C-11-deuterium-L-deprenyl (DED) and F-18-fluorodeoxyglucose (FDG) respectively in presymptomatic and symptomatic ADAD participants (n = 21), patients with mild cognitive impairment (n = 11) and sporadic AD (n = 7). Multivariate analysis using the combined data from all radiotracers clearly separated the different groups along the first and second principal components according to increased PIB retention/decreased FDG uptake (component 1) and increased DED binding (component 2). Presymptomatic ADAD mutation carriers showed significantly higher PIB retention than non-carriers in all brain regions except the hippocampus. DED binding was highest in presymptomatic ADAD mutation carriers. This suggests that non-fibrillar A beta or early stage plaque depostion might interact with inflammatory responses indicating astrocytosis as an early contributory driving force in AD pathology. The novelty of this finding will be investigated in longitudinal follow-up studies.

Place, publisher, year, edition, pages
2015. Vol. 5, 16404
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-268400DOI: 10.1038/srep16404ISI: 000364446700002PubMedID: 26553227OAI: oai:DiVA.org:uu-268400DiVA: diva2:878515
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council, 05817Swedish Research Council, 521-2010-3134Stockholm County CouncilThe Karolinska Institutet's Research FoundationSwedish Foundation for Strategic Research The Swedish Brain Foundation
Available from: 2015-12-09 Created: 2015-12-04 Last updated: 2017-12-01Bibliographically approved

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Wall, AndersLångström, Bengt

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