Lowering levels of reelin in entorhinal cortex layer II-neurons results in lowered levels of intracellular amyloid-β

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: onr:"swepub:oai:lup.lub.lu.se:55bb2ae8-1a7a-4fe7-9f21-b7dc8d0bf30d" > Lowering levels of ...

1 of 1
Previous record
Next record
To hitlist

Details
MARC

Kobro-Flatmoen, AsgeirNorwegian University of Science and Technology (author)

Lowering levels of reelin in entorhinal cortex layer II-neurons results in lowered levels of intracellular amyloid-β

Article/chapterEnglish2023

Publisher, publication year, extent ...

2023

Numbers

LIBRIS-ID:oai:lup.lub.lu.se:55bb2ae8-1a7a-4fe7-9f21-b7dc8d0bf30d
https://lup.lub.lu.se/record/55bb2ae8-1a7a-4fe7-9f21-b7dc8d0bf30dURI
https://doi.org/10.1093/braincomms/fcad115DOI

Supplementary language notes

Language:English
Summary in:English

Part of subdatabase

SwePubSwePub

Classification

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

Notes

Projection neurons in the anteriolateral part of entorhinal cortex layer II are the predominant cortical site for hyper-phosphorylation of tau and formation of neurofibrillary tangles in prodromal Alzheimer's disease. A majority of layer II projection neurons in anteriolateral entorhinal cortex are unique among cortical excitatory neurons by expressing the protein reelin. In prodromal Alzheimer's disease, these reelin-expressing neurons are prone to accumulate intracellular amyloid-β, which is mimicked in a rat model that replicates the spatio-temporal cascade of the disease. Two important findings in relation to this are that reelin-signalling downregulates tau phosphorylation, and that oligomeric amyloid-β interferes with reelin-signalling. Taking advantage of this rat model, we used proximity ligation assay to assess whether reelin and intracellular amyloid-β directly interact during early, pre-plaque stages in anteriolateral entorhinal cortex layer II reelin-expressing neurons. We next made a viral vector delivering micro-RNA against reelin, along with a control vector, and infected reelin-expressing anteriolateral entorhinal cortex layer II-neurons to test whether reelin levels affect levels of intracellular amyloid-β and/or amyloid precursor protein. We analysed 25.548 neurons from 24 animals, which results in three important findings. First, in reelin-expressing anteriolateral entorhinal cortex layer II-neurons, reelin and intracellular amyloid-β engage in a direct protein-protein interaction. Second, injecting micro-RNA against reelin lowers reelin levels in these neurons, amounting to an effect size of 1.3-4.5 (Bayesian estimation of Cohen's d effect size, 95% credible interval). This causes a concomitant reduction of intracellular amyloid-β ranging across three levels of aggregation, including a reduction of Aβ42 monomers/dimers amounting to an effect size of 0.5-3.1, a reduction of Aβ prefibrils amounting to an effect size of 1.1-3.5 and a reduction of protofibrils amounting to an effect size of 0.05-2.1. Analysing these data using Bayesian estimation of mutual information furthermore reveals that levels of amyloid-β are dependent on levels of reelin. Third, the reduction of intracellular amyloid-β occurs without any substantial associated changes in levels of amyloid precursor protein. We conclude that reelin and amyloid-β directly interact at the intracellular level in the uniquely reelin-expressing projection neurons in anteriolateral entorhinal cortex layer II, where levels of amyloid-β are dependent on levels of reelin. Since amyloid-β is known to impair reelin-signalling causing upregulated phosphorylation of tau, our findings are likely relevant to the vulnerability for neurofibrillary tangle-formation of this entorhinal neuronal population.

Subject headings and genre

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

Battistin, ClaudiaNorwegian University of Science and Technology (author)
Nair, Rajeevkumar RaveendranNorwegian University of Science and Technology (author)
Bjorkli, ChristianaNorwegian University of Science and Technology (author)
Skender, BelmaNorwegian University of Science and Technology (author)
Kentros, CliffNorwegian University of Science and Technology (author)
Gouras, GunnarLund University,Lunds universitet,Experimentell demensforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Experimental Dementia Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas(Swepub:lu)med-grg (author)
Witter, Menno PNorwegian University of Science and Technology (author)
Norwegian University of Science and TechnologyExperimentell demensforskning (creator_code:org_t)

Related titles

In:Brain Communications5:2, s. 1-152632-1297

Internet link

Find in a library

Brain Communications (Search for host publication in LIBRIS)

To the university's database

1 of 1
Previous record
Next record
To hitlist

Find more in SwePub

By the author/editor: Kobro-Flatmoen, ...; Battistin, Claud ...; Nair, Rajeevkuma ...; Bjorkli, Christi ...; Skender, Belma; Kentros, Cliff; show more...; Gouras, Gunnar; Witter, Menno P; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

Articles in the publication: Brain Communicat ...

By the university: Lund University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se