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Astroglial Responses to Amyloid-Beta Progression in a Mouse Model of Alzheimer's Disease
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Geriatrik.
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2018 (Engelska)Ingår i: Molecular Imaging and Biology, ISSN 1536-1632, E-ISSN 1860-2002, Vol. 20, nr 4, s. 605-614Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-beta (A beta) deposition, hyperphosphorylation of tau, and neuroinflammation. Astrocytes, the most abundant glial cell type in the nervous system, respond to neurodegenerative disorders through astrogliosis, i.e., converting to a reactive inflammatory state. The aim of this study was to investigate how in vivo quantification of astrogliosis using positron emission tomography (PET) radioligand deuterium-l-[C-11]deprenyl ([C-11]DED), binding to enzyme monoamine oxidase-B (MAO-B) which is overexpressed in reactive astrocytes during AD, corresponds to expression of glial fibrillary acidic protein (GFAP) and vimentin, i.e., two well-established markers of astrogliosis, during A beta pathology progression. APP(ArcSwe) mice (n = 37) and wild-type (WT) control mice (n = 23), 2-16-month old, were used to investigate biomarkers of astrogliosis. The radioligand, [C-11]DED, was used as an in vivo marker while GFAP, vimentin, and MAO-B were used to investigate astrogliosis and macrophage-associated lectin (Mac-2) to investigate microglia/macrophage activation by immunohistochemistry of the mouse brain. A beta and GFAP levels were also measured with ELISA in brain homogenates. The intrabrain levels of aggregated A beta and reactive astrocytes were found to be elevated in APP(ArcSwe) compared with WT mice. GFAP and vimentin expression increased with age, i.e., with A beta pathology, in the APP(ArcSwe) mice. This was not the case for in vivo marker [C-11]DED that showed elevated binding of the same magnitude in APP(ArcSwe) mice compared with WT mice at both 8 and 16 months. Further, immunohistochemistry indicated that there was limited co-expression of MAO-B and GFAP. MAO-B levels are increased early in A beta pathology progression, while GFAP and vimentin appear to increase later, most likely as a consequence of abundant A beta plaque formation. Thus, [C-11]DED is a useful PET radioligand for the detection of changes in MAO-B at an early stage of AD progression but does not measure the total extent of astrogliosis at advanced stages of A beta pathology.

Ort, förlag, år, upplaga, sidor
SPRINGER , 2018. Vol. 20, nr 4, s. 605-614
Nyckelord [en]
PET, Amyloid-beta, Astrocytes, Astrogliosis, MAO-B, GFAP, Vimentin, [C-11]DED
Nationell ämneskategori
Neurovetenskaper Neurologi
Identifikatorer
URN: urn:nbn:se:uu:diva-361033DOI: 10.1007/s11307-017-1153-zISI: 000438457800010PubMedID: 29297157OAI: oai:DiVA.org:uu-361033DiVA, id: diva2:1250181
Forskningsfinansiär
HjärnfondenGun och Bertil Stohnes StiftelseTillgänglig från: 2018-09-21 Skapad: 2018-09-21 Senast uppdaterad: 2018-09-21Bibliografiskt granskad

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