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Interictal spikes during sleep are an early defect in the Tg2576 mouse model of β-amyloid neuropathology
Kam K, Duffy ÁM, Moretto J, LaFrancois JJ, Scharfman HE.. Scientific reports, 2016-01-28
Topic: Brain proteins, microglia and lab models
It has been suggested that neuronal hyperexcitability contributes to Alzheimer's disease (AD), so we asked how hyperexcitability develops in a common mouse model of β-amyloid neuropathology - Tg2576 mice. Using video-EEG recordings, we found synchronized, large amplitude potentials resembling interictal spikes (IIS) in epilepsy at just 5 weeks of age, long before memory impairments or β-amyloid deposition. Seizures were not detected, but they did occur later in life, suggesting that IIS are possibly the earliest stage of hyperexcitability. Interestingly, IIS primarily occurred during rapid-eye movement (REM) sleep, which is notable because REM is associated with increased cholinergic tone and cholinergic impairments are implicated in AD. Although previous studies suggest that cholinergic antagonists would worsen pathophysiology, the muscarinic antagonist atropine reduced IIS frequency. In addition, we found IIS occurred in APP51 mice which overexpress wild type (WT)-APP, although not as uniformly or as early in life as Tg2576 mice. Taken together with results from prior studies, the data suggest that surprising and multiple mechanisms contribute to hyperexcitability. The data also suggest that IIS may be a biomarker for early detection of AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Kam, K., ÁM, D., Moretto, J., LaFrancois, J. J., & Scharfman, H. E. (2016). Interictal spikes during sleep are an early defect in the Tg2576 mouse model of β-amyloid neuropathology. Scientific reports. https://doi.org/10.1038/srep20119
Vancouver
Kam K, ÁM D, Moretto J, LaFrancois JJ, Scharfman HE. Interictal spikes during sleep are an early defect in the Tg2576 mouse model of β-amyloid neuropathology. Scientific reports. 2016. doi:10.1038/srep20119. PMID: 26818394.
BibTeX
@article{kam2016-26818394,
author = {Kam, K. and ÁM, Duffy and Moretto, J. and LaFrancois, J. J. and Scharfman, H. E.},
title = {{Interictal spikes during sleep are an early defect in the Tg2576 mouse model of β-amyloid neuropathology}},
journal = {Scientific reports},
year = {2016},
doi = {10.1038/srep20119},
pmid = {26818394},
url = {https://doi.org/10.1038/srep20119}
}
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Key findings
- It has been suggested that neuronal hyperexcitability contributes to Alzheimer's disease (AD), so we asked how hyperexcitability develops in a common mouse model of β-amyloid neuropathology - Tg2576 mice.
- Using video-EEG recordings, we found synchronized, large amplitude potentials resembling interictal spikes (IIS) in epilepsy at just 5 weeks of age, long before memory impairments or β-amyloid deposition.
- Seizures were not detected, but they did occur later in life, suggesting that IIS are possibly the earliest stage of hyperexcitability.
- Interestingly, IIS primarily occurred during rapid-eye movement (REM) sleep, which is notable because REM is associated with increased cholinergic tone and cholinergic impairments are implicated in AD.
- Although previous studies suggest that cholinergic antagonists would worsen pathophysiology, the muscarinic antagonist atropine reduced IIS frequency.
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Study details
- Evidence strengthLow
How this study scored 40/100
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 23 of the 58 points we could judge it on, which is 40 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 | 1 / 5 | 2016 — within 20 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 “tg2576”) — 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 26818394) |
| Free to read | 2 / 2 | Free to read |
| Points | 23 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 23 of the 58 points we could judge it on is 40 out of 100. |
| Total | 40 / 100 | — |
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