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Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by C-11-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining C-11-Pittsburgh Compound B and F-18-FDG
Stockholms universitet, Samhällsvetenskapliga fakulteten, Psykologiska institutionen. Karolinska Institutet, Sweden.
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Antal upphovsmän: 72012 (Engelska)Ingår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 53, nr 1, s. 37-46Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Astrocytes colocalize with fibrillar amyloid-beta (A beta) plaques in postmortem Alzheimer disease (AD) brain tissue. It is therefore of great interest to develop a PET tracer for visualizing astrocytes in vivo, enabling the study of the regional distribution of both astrocytes and fibrillar A beta. A multitracer PET investigation was conducted for patients with mild cognitive impairment (MCI), patients with mild AD, and healthy controls using C-11-deuterium-L-deprenyl (C-11-DED) to measure monoamine oxidase B located in astrocytes. Along with C-11-DED PET, C-11-Pittsburgh compound B (C-11-PIB; fibrillar A beta deposition), F-18-FDG (glucose metabolism), T1 MRI, cerebrospinal fluid, and neuropsychologic data were acquired from the patients. Methods: C-11-DED PET was performed in MCI patients (n = 8; mean age 6 SD, 62.6 +/- 7.5 y; mean Mini Mental State Examination, 27.5 +/- 2.1), AD patients (n = 7; mean age, 65.1 +/- 6.3 y; mean Mini Mental State Examination, 24.4 +/- 5.7), and healthy age-matched controls (n = 14; mean age, 64.7 +/- 3.6 y). A modified reference Patlak model, with cerebellar gray matter as a reference, was chosen for kinetic analysis of the C-11-DED data. C-11-DED data from 20 to 60 min were analyzed using a digital brain atlas. Mean regional F-18-FDG uptake and C-11-PIB retention were calculated for each patient, with cerebellar gray matter as a reference. Results: ANOVA analysis of the regional C-11-DED binding data revealed a significant group effect in the bilateral frontal and bilateral parietal cortices related to increased binding in the MCI patients. All patients, except 3 with MCI, showed high C-11-PIB retention. Increased C-11-DED binding in most cortical and subcortical regions was observed in MCI C-11-PIB+ patients relative to controls, MCI C-11-PIB (negative) patients, and AD patients. No regional correlations were found between the 3 PET tracers. Conclusion: Increased C-11-DED binding throughout the brain of the MCI C-11-PIB+ patients potentially suggests that astrocytosis is an early phenomenon in AD development.

Ort, förlag, år, upplaga, sidor
2012. Vol. 53, nr 1, s. 37-46
Nyckelord [en]
Alzheimer disease, mild cognitive impairment, PET, astrocytosis, amyloid, monoamine oxidase B
Nationell ämneskategori
Neurologi Radiologi och bildbehandling
Identifikatorer
URN: urn:nbn:se:su:diva-168103DOI: 10.2967/jnumed.110.087031ISI: 000298660900018PubMedID: 22213821OAI: oai:DiVA.org:su-168103DiVA, id: diva2:1305604
Tillgänglig från: 2019-04-17 Skapad: 2019-04-17 Senast uppdaterad: 2019-04-17Bibliografiskt granskad

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Carter, Stephen F.Schöll, MichaelAlmkvist, Ove
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Psykologiska institutionen
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Journal of Nuclear Medicine
NeurologiRadiologi och bildbehandling

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