Evidence map›Paper›PMID 34232476›Full record

ArticleMolecular neurobiology2021

Precocious White Matter Inflammation and Behavioural Inflexibility Precede Learning and Memory Impairment in the TgAPP21 Rat Model of Alzheimer Disease.

Alexander Levit, Andrew Gibson, Olivia Hough, Youngkyung Jung, Yuksel Agca, Cansu Agca, Vladimir Hachinski, Brian L Allman, Shawn N Whitehead

Abstract read
PubMed Publisher
In one paragraph

Article in Molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.7field-weighted citation impact, top 31% 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

2 citing papers in PubMed, 9 citations in OpenAlex.

  1. Increased circulating TREM2Brain, behavior, & immunity - health · 2026
    Article
  2. Article
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 at 2 institutions in 2 countries.

Alexander LevitVulnerable Brain Laboratory, Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.ORCID http://orcid.org/0000-0003-2921-4339
Andrew GibsonVulnerable Brain Laboratory, Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
Olivia HoughVulnerable Brain Laboratory, Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
Youngkyung JungVulnerable Brain Laboratory, Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
Yuksel AgcaDepartment of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, MO, USA.ORCID http://orcid.org/0000-0002-9883-3291
Cansu AgcaDepartment of Veterinary Pathobiology, University of Missouri College of Veterinary Medicine, Columbia, MO, USA.ORCID http://orcid.org/0000-0001-6641-7448
Vladimir HachinskiDepartment of Clinical Neurological Sciences, University Hospital, University of Western Ontario, London, ON, N6A 5C1, Canada.ORCID http://orcid.org/0000-0002-0487-734X
Brian L AllmanVulnerable Brain Laboratory, Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.ORCID http://orcid.org/0000-0001-8793-2019
Shawn N WhiteheadVulnerable Brain Laboratory, Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada. Shawn.Whitehead@schulich.uwo.ca.ORCID http://orcid.org/0000-0003-4728-8067
Western University · CAMissouri College · US

Funding

Canadian Foundation for Innovation 34213CIHR 126127Natural Sciences and Engineering Research Council 418489Natural Sciences and Engineering Research Council of Canada 435819
6 · The paper itself

Abstract

Neuroinflammation and behavioural inflexibility are both common in late adulthood but far more profound in Alzheimer disease (AD). To investigate the relationship between ageing, AD, neuroinflammation, and behavioural flexibility, male wild-type Fischer 344 (Wt) and the transgenic APP21 (TgAPP21) rats were aged to 4, 8, 13, and 22 months and evaluated for neuroinflammation and cognitive impairment. TgAPP21 rats overexpress a pathogenic variant of the human amyloid precursor protein (hAPP; Swedish and Indiana mutations) but do not spontaneously develop overt pathology related to AD. In both genotypes, learning and memory were similarly impaired in older rats. However, at 8 months of age, TgAPP21 rats demonstrated behavioural inflexibility in set shifting, reversal, and the Morris water maze, while Wt rats showed inflexibility at 13 and 22 months of age. This early inflexibility in TgAPP21 rats was accompanied by a precocious increase in microglia activation within the corpus callosum; 8- and 13-month-old TgAPP21 rats had similar levels of microglia activation as 13- and 22-month-old Wt rats, respectively. However, while neuroinflammation within the white matter continued to progress with age, behavioural inflexibility peaked in 8-month-old TgAPP21 rats; in older TgAPP21 rats, memory and learning impairments masked inflexibility. These findings suggest that the behavioural inflexibility and white matter inflammation seen in normal ageing are accelerated in AD and may precede impairments of learning and memory.

Indexed as

AgingAlzheimer DiseaseAnimalsCorpus CallosumDiscrimination LearningDisease Models, AnimalMaleMaze LearningMemory DisordersRatsRats, Inbred F344Rats, TransgenicWhite MatterAgeingAlzheimer diseaseBehavioral flexibilityExecutive functionMicrogliaWhite matter

Identifiers

PMID34232476
OpenAlexW3180235918

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.