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Medin co-aggregates...
Medin co-aggregates with vascular amyloid-beta in Alzheimers disease
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- Wagner, Jessica (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany; Univ Tubingen, Germany
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- Degenhardt, Karoline (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany; Univ Tubingen, Germany
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- Veit, Marleen (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany; Univ Tubingen, Germany
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- Louros, Nikolaos (författare)
- VIB KU Leuven Ctr Brain & Dis Res, Belgium; Katholieke Univ Leuven, Belgium
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- Konstantoulea, Katerina (författare)
- VIB KU Leuven Ctr Brain & Dis Res, Belgium; Katholieke Univ Leuven, Belgium
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- Skodras, Angelos (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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- Wild, Katleen (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany
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- Liu, Ping (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany; Univ Tubingen, Germany
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- Obermueller, Ulrike (författare)
- Univ Tubingen, Germany
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- Bansal, Vikas (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany
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- Dalmia, Anupriya (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany
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- Haesler, Lisa M. (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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- Lambert, Marius (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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- De Vleeschouwer, Matthias (författare)
- VIB KU Leuven Ctr Brain & Dis Res, Belgium; Katholieke Univ Leuven, Belgium
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- Davies, Hannah A. (författare)
- Univ Liverpool, England; Univ Liverpool, England
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- Madine, Jillian (författare)
- Univ Liverpool, England; Univ Liverpool, England
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- Kronenberg-Versteeg, Deborah (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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- Feederle, Regina (författare)
- Helmholtz Zentrum Munchen, Germany; German Ctr Neurodegenerat Dis DZNE, Germany
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- Del Turco, Domenico (författare)
- Goethe Univ, Germany
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- Nilsson, Peter, 1970- (författare)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Lashley, Tammaryn (författare)
- UCL, England; UCL, England
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- Deller, Thomas (författare)
- Goethe Univ, Germany
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- Gearing, Marla (författare)
- Emory Univ, GA 30322 USA; Emory Univ, GA 30322 USA
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- Walker, Lary C. (författare)
- Emory Univ, GA 30322 USA; Emory Univ, GA 30322 USA
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- Heutink, Peter (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany
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- Rousseau, Frederic (författare)
- VIB KU Leuven Ctr Brain & Dis Res, Belgium; Katholieke Univ Leuven, Belgium
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- Schymkowitz, Joost (författare)
- VIB KU Leuven Ctr Brain & Dis Res, Belgium; Katholieke Univ Leuven, Belgium
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- Jucker, Mathias (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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- Neher, Jonas J. (författare)
- German Ctr Neurodegenerat Dis DZNE, Germany; Univ Tubingen, Germany
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(creator_code:org_t)
- 2022-11-16
- 2022
- Engelska.
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Ingår i: Nature. - : Nature Portfolio. - 0028-0836 .- 1476-4687. ; 612, s. 123-131
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Aggregates of medin amyloid (a fragment of the protein MFG-E8, also known as lactadherin) are found in the vasculature of almost all humans over 50 years of age(1,)(2), making it the most common amyloid currently known. We recently reported that medin also aggregates in blood vessels of ageing wild-type mice, causing cerebrovascular dysfunction(3). Here we demonstrate in amyloid-beta precursor protein (APP) transgenic mice and in patients with Alzheimers disease that medin co-localizes with vascular amyloid-beta deposits, and that in mice, medin deficiency reduces vascular amyloid-beta deposition by half. Moreover, in both the mouse and human brain, MFG-E8 is highly enriched in the vasculature and both MFG-E8 and medin levels increase with the severity of vascular amyloid-beta burden. Additionally, analysing data from 566 individuals in the ROSMAP cohort, we find that patients with Alzheimers disease have higher MFGE8 expression levels, which are attributable to vascular cells and are associated with increased measures of cognitive decline, independent of plaque and tau pathology. Mechanistically, we demonstrate that medin interacts directly with amyloid-beta to promote its aggregation, as medin forms heterologous fibrils with amyloid-beta, affects amyloid-beta fibril structure, and cross-seeds amyloid-beta aggregation both in vitro and in vivo. Thus, medin could be a therapeutic target for prevention of vascular damage and cognitive decline resulting from amyloid-beta deposition in the blood vessels of the brain.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
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Nature
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- Av författaren/redakt...
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Wagner, Jessica
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Degenhardt, Karo ...
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Veit, Marleen
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Louros, Nikolaos
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Konstantoulea, K ...
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Skodras, Angelos
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visa fler...
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Wild, Katleen
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Liu, Ping
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Obermueller, Ulr ...
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Bansal, Vikas
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Dalmia, Anupriya
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Haesler, Lisa M.
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Lambert, Marius
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De Vleeschouwer, ...
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Davies, Hannah A ...
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Madine, Jillian
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Kronenberg-Verst ...
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Feederle, Regina
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Del Turco, Domen ...
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Nilsson, Peter, ...
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Lashley, Tammary ...
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Deller, Thomas
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Gearing, Marla
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Walker, Lary C.
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Heutink, Peter
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Rousseau, Freder ...
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Schymkowitz, Joo ...
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Jucker, Mathias
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Neher, Jonas J.
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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Linköpings universitet