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  • Verma, N. (author)

A beta efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023-01-03
  • Springer Science and Business Media LLC,2023

Numbers

  • LIBRIS-ID:oai:gup.ub.gu.se/324149
  • https://gup.ub.gu.se/publication/324149URI
  • https://doi.org/10.1038/s42003-022-04398-2DOI

Supplementary language notes

  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Velmurugan, G. V. (author)
  • Winford, E. (author)
  • 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)
  • 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)
  • Hardy, J. (author)
  • Lashley, T. (author)
  • Despa, F. (author)
  • Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi (creator_code:org_t)

Related titles

  • In:Communications Biology: Springer Science and Business Media LLC6:12399-3642

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