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

Publication ,  Journal Article
Verma, N; Velmurugan, GV; Winford, E; Coburn, H; Kotiya, D; Leibold, N; Radulescu, L; Despa, S; Chen, KC; Van Eldik, LJ; Nelson, PT; Jicha, GA ...
Published in: Commun Biol
January 3, 2023

Impairment of vascular pathways of cerebral β-amyloid (Aβ) 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 Aβ clearance. Blood amylin concentrations are higher in AD than in cognitively unaffected persons. Amyloid-forming amylin accumulates in circulating monocytes and co-deposits with Aβ within the brain microvasculature, possibly involving inflammation. In rats, pancreatic expression of amyloid-forming human amylin indeed induces cerebrovascular inflammation and amylin-Aβ co-deposits. LRP1-mediated Aβ transport across the blood-brain barrier and Aβ clearance through interstitial fluid drainage along vascular walls are impaired, as indicated by Aβ 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 Aβ pathology.

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Published In

Commun Biol

DOI

EISSN

2399-3642

Publication Date

January 3, 2023

Volume

6

Issue

1

Start / End Page

2

Location

England

Related Subject Headings

  • Rats
  • Pancreas
  • Islet Amyloid Polypeptide
  • Inflammation
  • Humans
  • Animals
  • Amyloidogenic Proteins
  • Amyloid beta-Peptides
  • Alzheimer Disease
  • 32 Biomedical and clinical sciences
 

Citation

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Verma, N., Velmurugan, G. V., Winford, E., Coburn, H., Kotiya, D., Leibold, N., … Despa, F. (2023). Aβ efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas. Commun Biol, 6(1), 2. https://doi.org/10.1038/s42003-022-04398-2
Verma, Nirmal, Gopal Viswanathan Velmurugan, Edric Winford, Han Coburn, Deepak Kotiya, Noah Leibold, Laura Radulescu, et al. “Aβ efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas.Commun Biol 6, no. 1 (January 3, 2023): 2. https://doi.org/10.1038/s42003-022-04398-2.
Verma N, Velmurugan GV, Winford E, Coburn H, Kotiya D, Leibold N, et al. Aβ efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas. Commun Biol. 2023 Jan 3;6(1):2.
Verma, Nirmal, et al. “Aβ efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas.Commun Biol, vol. 6, no. 1, Jan. 2023, p. 2. Pubmed, doi:10.1038/s42003-022-04398-2.
Verma N, Velmurugan GV, Winford E, Coburn H, Kotiya D, Leibold N, Radulescu L, Despa S, Chen KC, Van Eldik LJ, Nelson PT, Wilcock DM, Jicha GA, Stowe AM, Goldstein LB, Powel DK, Walton JH, Navedo MF, Nystoriak MA, Murray AJ, Biessels GJ, Troakes C, Zetterberg H, Hardy J, Lashley T, Despa F. Aβ efflux impairment and inflammation linked to cerebrovascular accumulation of amyloid-forming amylin secreted from pancreas. Commun Biol. 2023 Jan 3;6(1):2.

Published In

Commun Biol

DOI

EISSN

2399-3642

Publication Date

January 3, 2023

Volume

6

Issue

1

Start / End Page

2

Location

England

Related Subject Headings

  • Rats
  • Pancreas
  • Islet Amyloid Polypeptide
  • Inflammation
  • Humans
  • Animals
  • Amyloidogenic Proteins
  • Amyloid beta-Peptides
  • Alzheimer Disease
  • 32 Biomedical and clinical sciences