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Spatial reversal learning defect coincides with hypersynchronous telencephalic BOLD functional connectivity in APP NL-F/NL-F knock-in mice
Shah D, Latif-Hernandez A, De Strooper B, Saito T, Saido T, Verhoye M, D'Hooge R, Van der Linden A.. Scientific reports, 2018-04-19
Topic: Disease mechanisms in lab and animal studies
Amyloid pathology occurs early in Alzheimer's disease (AD), and has therefore been the focus of numerous studies. Transgenic mouse models have been instrumental to study amyloidosis, but observations might have been confounded by APP-overexpression artifacts. The current study investigated early functional defects in an APP knock-in mouse model, which allows assessing the effects of pathological amyloid-beta (Aβ) without interference of APP-artifacts. Female APP NL/NL knock-in mice of 3 and 7 months old were compared to age-matched APP NL-F/NL-F mice with increased Aβ42/40 ratio and initial Aβ-plaque deposition around 6 months of age. Spatial learning was examined using a Morris water maze protocol consisting of acquisition and reversal trials interleaved with reference memory tests. Functional connectivity (FC) of brain networks was assessed using resting-state functional MRI (rsfMRI). The Morris water maze data revealed that 3 months old APP NL-F/NL-F mice were unable to reach the same reference memory proficiency as APP NL/NL mice after reversal training. This cognitive defect in 3-month-old APP NL-F/NL-F mice coincided with hypersynchronous FC of the hippocampal, cingulate, caudate-putamen, and default-mode-like networks. The occurrence of these defects in APP NL-F/NL-F mice demonstrates that cognitive flexibility and synchronicity of telencephalic activity are specifically altered by early Aβ pathology without changes in APP neurochemistry.
Key findings
- Female APP NL/NL knock-in mice of 3 and 7 months old were compared to age-matched APP NL-F/NL-F mice with increased Aβ42/40 ratio and initial Aβ-plaque deposition around 6 months of age.
- The Morris water maze data revealed that 3 months old APP NL-F/NL-F mice were unable to reach the same reference memory proficiency as APP NL/NL mice after reversal training.
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Study details
- Evidence strengthLow
How this study scored 41/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 24 of the 58 points we could judge it on, which is 41 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Scientific reports) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mice”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29674739) |
| Free to read | 2 / 2 | Free to read |
| Points | 24 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 24 of the 58 points we could judge it on is 41 out of 100. |
| Total | 41 / 100 | — |
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Shah, D., Latif-Hernandez, A., De Strooper, B., Saito, T., Saido, T., Verhoye, M., et al. (2018). Spatial reversal learning defect coincides with hypersynchronous telencephalic BOLD functional connectivity in APP NL-F/NL-F knock-in mice. Scientific reports. https://doi.org/10.1038/s41598-018-24657-9
Vancouver
Shah D, Latif-Hernandez A, De Strooper B, Saito T, Saido T, Verhoye M, et al. Spatial reversal learning defect coincides with hypersynchronous telencephalic BOLD functional connectivity in APP NL-F/NL-F knock-in mice. Scientific reports. 2018. doi:10.1038/s41598-018-24657-9. PMID: 29674739.
BibTeX
@article{shah2018-29674739,
author = {Shah, D. and Latif-Hernandez, A. and De Strooper, B. and Saito, T. and Saido, T. and Verhoye, M. and D'Hooge, R. and Van der Linden, A.},
title = {{Spatial reversal learning defect coincides with hypersynchronous telencephalic BOLD functional connectivity in APP NL-F/NL-F knock-in mice}},
journal = {Scientific reports},
year = {2018},
doi = {10.1038/s41598-018-24657-9},
pmid = {29674739},
url = {https://doi.org/10.1038/s41598-018-24657-9}
}