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A beta efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas
- Verma, N. (author)
- Velmurugan, G. V. (author)
- Winford, E. (author)
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- Coburn, H. (author)
- Kotiya, D. (author)
- Leibold, N. (author)
- Radulescu, L. (author)
- Despa, S. (author)
- Chen, K. C. (author)
- Van Eldik, L. J. (author)
- Nelson, P. T. (author)
- Wilcock, D. M. (author)
- Jicha, G. A. (author)
- Stowe, A. M. (author)
- Goldstein, L. B. (author)
- Powel, D. K. (author)
- Walton, J. H. (author)
- Navedo, M. F. (author)
- Nystoriak, M. A. (author)
- Murray, A. J. (author)
- Biessels, G. J. (author)
- Troakes, C. (author)
- Hardy, J. (author)
- Lashley, T. (author)
- Despa, F. (author)
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- (creator_code:org_t)
- 2023-01-03
- 2023
- English.
- In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 6:1
- Journal article (peer-reviewed)
Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- alzheimers-disease patients
- brain insulin-resistance
- il-1-beta
- synthesis
- polypeptide
- cholesterol
- mechanisms
- clearance
- apoptosis
- correlate
- barrier
- Life Sciences & Biomedicine - Other Topics
- Science & Technology - Other
- Topics
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Verma, N.
- Velmurugan, G. V ...
- Winford, E.
- Coburn, H.
- Kotiya, D.
- Leibold, N.
- show more...
- Radulescu, L.
- Despa, S.
- Chen, K. C.
- Van Eldik, L. J.
- Nelson, P. T.
- Wilcock, D. M.
- Jicha, G. A.
- Stowe, A. M.
- Goldstein, L. B.
- Powel, D. K.
- Walton, J. H.
- Navedo, M. F.
- Nystoriak, M. A.
- Murray, A. J.
- Biessels, G. J.
- Troakes, C.
- Zetterberg, Henr ...
- Hardy, J.
- Lashley, T.
- Despa, F.
- show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Basic Medicine
- and Neurosciences
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- Communications B ...
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- University of Gothenburg
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