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A beta efflux impai...
A beta efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas
- Article/chapterEnglish2023
Publisher, publication year, extent ...
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2023-01-03
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Springer Science and Business Media LLC,2023
Numbers
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LIBRIS-ID:oai:gup.ub.gu.se/324149
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https://gup.ub.gu.se/publication/324149URI
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https://doi.org/10.1038/s42003-022-04398-2DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Impairment of vascular pathways of cerebral beta-amyloid (A beta) elimination contributes to Alzheimer disease (AD). Vascular damage is commonly associated with diabetes. Here we show in human tissues and AD-model rats that bloodborne islet amyloid polypeptide (amylin) secreted from the pancreas perturbs cerebral A beta clearance. Blood amylin concentrations are higher in AD than in cognitively unaffected persons. Amyloid-forming amylin accumulates in circulating monocytes and co-deposits with A beta within the brain microvasculature, possibly involving inflammation. In rats, pancreatic expression of amyloid-forming human amylin indeed induces cerebrovascular inflammation and amylin-A beta co-deposits. LRP1-mediated A beta transport across the blood-brain barrier and A beta clearance through interstitial fluid drainage along vascular walls are impaired, as indicated by A beta deposition in perivascular spaces. At the molecular level, cerebrovascular amylin deposits alter immune and hypoxia-related brain gene expression. These converging data from humans and laboratory animals suggest that altering bloodborne amylin could potentially reduce cerebrovascular amylin deposits and A beta pathology.
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Velmurugan, G. V.
(author)
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Winford, E.
(author)
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Coburn, H.
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Kotiya, D.
(author)
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Leibold, N.
(author)
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Radulescu, L.
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Despa, S.
(author)
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Chen, K. C.
(author)
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Van Eldik, L. J.
(author)
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Nelson, P. T.
(author)
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Wilcock, D. M.
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Jicha, G. A.
(author)
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Stowe, A. M.
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Goldstein, L. B.
(author)
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Powel, D. K.
(author)
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Walton, J. H.
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Navedo, M. F.
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Nystoriak, M. A.
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Murray, A. J.
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Biessels, G. J.
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Troakes, C.
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Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xzethe
(author)
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Hardy, J.
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Lashley, T.
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Despa, F.
(author)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
(creator_code:org_t)
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In:Communications Biology: Springer Science and Business Media LLC6:12399-3642
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Verma, N.
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Velmurugan, G. V ...
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Winford, E.
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Coburn, H.
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Kotiya, D.
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Leibold, N.
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show more...
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Radulescu, L.
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Despa, S.
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Chen, K. C.
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Van Eldik, L. J.
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Nelson, P. T.
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Wilcock, D. M.
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Jicha, G. A.
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Stowe, A. M.
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Goldstein, L. B.
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Powel, D. K.
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Walton, J. H.
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Navedo, M. F.
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Nystoriak, M. A.
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Murray, A. J.
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Biessels, G. J.
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Troakes, C.
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Zetterberg, Henr ...
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Hardy, J.
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Lashley, T.
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Despa, F.
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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Communications B ...
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University of Gothenburg