Evidence mapPaperPMID 36596993Full record

ArticleCommunications biology2023

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

Nirmal Verma, Gopal Viswanathan Velmurugan, Edric Winford, Han Coburn, Deepak Kotiya, Noah Leibold, Laura Radulescu, Sanda Despa, Kuey C Chen, Linda J Van Eldik and 16 more

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 21 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 10 institutions in 6 countries.

Nirmal Verma *Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Gopal Viswanathan Velmurugan *Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Edric WinfordDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Han CoburnDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Deepak KotiyaDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Noah LeiboldDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Laura RadulescuDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Sanda DespaDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Kuey C ChenDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA.
Linda J Van EldikSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.ORCID 0000-0002-8139-6400
Peter T NelsonSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
Donna M WilcockSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
Gregory A JichaSanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
Ann M StoweDepartment of Neurology, University of Kentucky, Lexington, KY, USA.
Larry B GoldsteinDepartment of Neurology, University of Kentucky, Lexington, KY, USA.ORCID 0000-0001-7747-128X
David K PowelMagnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY, USA.
Jeffrey H WaltonNMR Facility, University of California, Davis, CA, USA.ORCID 0000-0002-2359-955X
Manuel F NavedoDepartment of Pharmacology, University of California, Davis, CA, USA.ORCID 0000-0001-6864-6594
Matthew A NystoriakDepartment of Medicine, University of Louisville, Louisville, KY, USA.ORCID 0000-0001-8872-158X
Andrew J MurrayDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 3EG, UK.ORCID 0000-0002-0929-9315
Geert Jan BiesselsDepartment of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID 0000-0001-6862-2496
Claire TroakesBasic and Clinical Neuroscience Department, King's College London, London, UK.ORCID 0000-0002-1790-7376
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
John HardyDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Tammaryn LashleyDepartment of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Florin DespaDepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA. f.despa@uky.edu.ORCID 0000-0002-5879-6449
University of Kentucky · USUniversity of California, Davis · USKing's College London · GBNational Hospital for Neurology and Neurosurgery · GBQueen Mary University of London · GBSahlgrenska University Hospital · SEUniversity Medical Center Utrecht · NLUniversity of Cambridge · GBUniversity of Kentucky HealthCare · USUniversity of Louisville · US

Funding

University of Kentucky Alzheimer's Disease Research CenterP30AG072946 · UNIVERSITY OF KENTUCKY · 2025 to 2025
$2.8M
Medical Research Council MR/N026004/1NHLBI NIH HHS R01 HL118474NHLBI NIH HHS R01 HL149127NIA NIH HHS P30 AG028383NIA NIH HHS P30 AG072946NIA NIH HHS R01 AG053999NIA NIH HHS R01 AG057290NINDS NIH HHS R01 NS116058Wellcome Trust
6 · The paper itself

Abstract

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.

Indexed as

Alzheimer DiseaseIslet Amyloid PolypeptideAmyloid beta-PeptidesAmyloidogenic ProteinsAnimalsHumansInflammationPancreasRatsAmyloid beta-PeptidesAmyloidogenic ProteinsIslet Amyloid Polypeptide

Identifiers

PMID36596993
PMCPMC9810597
OpenAlexW4313528230

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.