Evidence map›Paper›PMID 30311654›Full record

ArticleThe Journal of comparative neurology2019

Whole brain imaging reveals distinct spatial patterns of amyloid beta deposition in three mouse models of Alzheimer's disease.

Jennifer D Whitesell, Alex R Buckley, Joseph E Knox, Leonard Kuan, Nile Graddis, Andrew Pelos, Alice Mukora, Wayne Wakeman, Phillip Bohn, Anh Ho and 2 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of comparative neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
5.9field-weighted citation impact, top 3% 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

52 citing papers in PubMed, 92 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

12 authors at 2 institutions in 1 country.

Jennifer D WhitesellAllen Institute for Brain Science, Seattle, Washington.ORCID 0000-0002-2961-5207
Alex R BuckleyWashington University in St. Louis.
Joseph E KnoxAllen Institute for Brain Science, Seattle, Washington.
Leonard KuanAllen Institute for Brain Science, Seattle, Washington.
Nile GraddisAllen Institute for Brain Science, Seattle, Washington.
Andrew PelosAllen Institute for Brain Science, Seattle, Washington.
Alice MukoraAllen Institute for Brain Science, Seattle, Washington.
Wayne WakemanAllen Institute for Brain Science, Seattle, Washington.
Phillip BohnAllen Institute for Brain Science, Seattle, Washington.
Anh HoAllen Institute for Brain Science, Seattle, Washington.
Karla E HirokawaAllen Institute for Brain Science, Seattle, Washington.
Julie A HarrisAllen Institute for Brain Science, Seattle, Washington.ORCID 0000-0003-0820-2021
Allen Institute for Brain Science · USWashington University in St. Louis · US

Funding

Mouse Cell Type-Specific Brain Mapping in Health and DiseaseR01AG047589 · NIA · ALLEN INSTITUTE · PI HARRIS, JULIE · 2014 to 2018
$3.4M
NIA NIH HHS R01 AG047589
6 · The paper itself

Abstract

A variety of Alzheimer's disease (AD) mouse models overexpress mutant forms of human amyloid precursor protein (APP), producing high levels of amyloid β (Aβ) and forming plaques. However, the degree to which these models mimic spatiotemporal patterns of Aβ deposition in brains of AD patients is unknown. Here, we mapped the spatial distribution of Aβ plaques across age in three APP-overexpression mouse lines (APP/PS1, Tg2576, and hAPP-J20) using in vivo labeling with methoxy-X04, high throughput whole brain imaging, and an automated informatics pipeline. Images were acquired with high resolution serial two-photon tomography and labeled plaques were detected using custom-built segmentation algorithms. Image series were registered to the Allen Mouse Brain Common Coordinate Framework, a 3D reference atlas, enabling automated brain-wide quantification of plaque density, number, and location. In both APP/PS1 and Tg2576 mice, plaques were identified first in isocortex, followed by olfactory, hippocampal, and cortical subplate areas. In hAPP-J20 mice, plaque density was highest in hippocampal areas, followed by isocortex, with little to no involvement of olfactory or cortical subplate areas. Within the major brain divisions, distinct regions were identified with high (or low) plaque accumulation; for example, the lateral visual area within the isocortex of APP/PS1 mice had relatively higher plaque density compared with other cortical areas, while in hAPP-J20 mice, plaques were densest in the ventral retrosplenial cortex. In summary, we show how whole brain imaging of amyloid pathology in mice reveals the extent to which a given model recapitulates the regional Aβ deposition patterns described in AD.

Indexed as

Amyloid beta-PeptidesAlzheimer DiseaseAnimalsBrainDisease Models, AnimalImage Processing, Computer-AssistedMiceMice, TransgenicNeuroimagingAmyloid beta-PeptidesAlzheimer's mouse modelamyloid betaplaque depositionRRID: AB_1977025RRID: AB_2535766RRID:IMSR_TAC:1349RRID:MMRRC_034832-JAXRRID:MMRRC_034836-JAXwhole brain imaging

Identifiers

PMID30311654
PMCPMC8026112
OpenAlexW2949152232

What OpenQuestion holds

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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 OpenQuestion graph.