Evidence map›Paper›PMID 28569090›Full record

ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2018

Insulin differentially affects the distribution kinetics of amyloid beta 40 and 42 in plasma and brain.

Suresh Kumar Swaminathan, Kristen M Ahlschwede, Vidur Sarma, Geoffry L Curran, Rajesh S Omtri, Teresa Decklever, Val J Lowe, Joseph F Poduslo, Karunya K Kandimalla

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In one paragraph

Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
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

32 citing papers in PubMed.

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  13. How Can Insulin Resistance Cause Alzheimer's Disease?International journal of molecular sciences · 2023
    Review
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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

9 authors.

Suresh Kumar Swaminathan1 Department of Pharmaceutics and Brain Barriers Research Center, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
Kristen M Ahlschwede1 Department of Pharmaceutics and Brain Barriers Research Center, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
Vidur Sarma1 Department of Pharmaceutics and Brain Barriers Research Center, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
Geoffry L Curran2 Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Rajesh S Omtri1 Department of Pharmaceutics and Brain Barriers Research Center, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
Teresa Decklever2 Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Val J Lowe2 Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Joseph F Poduslo3 Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Karunya K Kandimalla1 Department of Pharmaceutics and Brain Barriers Research Center, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Impaired brain clearance of amyloid-beta peptides (Aβ) 40 and 42 across the blood-brain barrier (BBB) is believed to be one of the pathways responsible for Alzheimer's disease (AD) pathogenesis. Hyperinsulinemia prevalent in type II diabetes was shown to damage cerebral vasculature and increase Aβ accumulation in AD brain. However, there is no clarity on how aberrations in peripheral insulin levels affect Aβ accumulation in the brain. This study describes, for the first time, an intricate relation between plasma insulin and Aβ transport at the BBB. Upon peripheral insulin administration in wild-type mice: the plasma clearance of Aβ40 increased, but Aβ42 clearance reduced; the plasma-to-brain influx of Aβ40 increased, and that of Aβ42 reduced; and the clearance of intracerebrally injected Aβ40 decreased, whereas Aβ42 clearance increased. In hCMEC/D3 monolayers (in vitro BBB model) exposed to insulin, the luminal uptake and luminal-to-abluminal permeability of Aβ40 increased and that of Aβ42 reduced; the abluminal-to-luminal permeability of Aβ40 decreased, whereas Aβ42 permeability increased. Moreover, Aβ cellular trafficking machinery was altered. In summary, Aβ40 and Aβ42 demonstrated distinct distribution kinetics in plasma and brain compartments, and insulin differentially modulated their distribution. Cerebrovascular disease and metabolic disorders may disrupt this intricate homeostasis and aggravate AD pathology.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAnimalsBlood-Brain BarrierBrain ChemistryCell LineHumansInsulinMicePeptide FragmentsProtein TransportTissue DistributionAmyloid beta-Peptidesamyloid beta-protein (1-40)amyloid beta-protein (1-42)InsulinPeptide FragmentsAlzheimer's diseaseblood–brain barriercerebrovascular diseasediabetesendotheliuminsulinpharmacokineticsSPECT

Identifiers

PMID28569090
PMCPMC5987944

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.