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Amyloid pathology and cognitive impairment in hAβ-KI and APPSAA-KI mouse models of Alzheimer's disease
Wenyan Lu, Francis Shue, Aishe Kurti, Suren Jeevaratnam, Jesse R Macyczko, Bhaskar Roy, Taha Izhar, Ni Wang et al.. Neurobiology of aging, 2024-10-19
Topic: Disease mechanisms in lab and animal studies
The hAβ-KI and APPSAA-KI are two amyloid models that harbor mutations in the endogenous mouse App gene. Both hAβ-KI and APPSAA-KI mice contain a humanized Aβ sequence, and APPSAA-KI mice carry three additional familial AD mutations. We herein report that the Aβ levels and Aβ42/Aβ40 ratio in APPSAA-KI homozygotes are dramatically higher than those in hAβ-KI homozygotes at 14 months of age. In addition, APPSAA-KI mice display a widespread distribution of amyloid plaques in the brain, whereas the plaques are undetectable in hAβ-KI mice. Moreover, there are no sex differences in amyloid pathology in APPSAA-KI mice. Both APPSAA-KI and hAβ-KI mice exhibit cognitive impairments, wherein no significant differences are found between these two models, although APPSAA KI mice show a trend towards worse cognitive function. Notably, female hAβ-KI and APPSAA-KI mice have a more pronounced cognitive impairments compared to their respective males. Our findings suggest that Aβ humanization contributes to cognitive deficits in APPSAA-KI mice, and that amyloid deposition might not be closely associated with cognitive impairments in APPSAA-KI mice.
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APA 7th
Lu, W., Shue, F., Kurti, A., Jeevaratnam, S., Macyczko, J. R., Roy, B., et al. (2025). Amyloid pathology and cognitive impairment in hAβ-KI and APPSAA-KI mouse models of Alzheimer's disease. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2024.10.005
Vancouver
Lu W, Shue F, Kurti A, Jeevaratnam S, Macyczko JR, Roy B, et al. Amyloid pathology and cognitive impairment in hAβ-KI and APPSAA-KI mouse models of Alzheimer's disease. Neurobiology of aging. 2025. doi:10.1016/j.neurobiolaging.2024.10.005. PMID: 39447490.
BibTeX
@article{lu2025-39447490,
author = {Lu, Wenyan and Shue, Francis and Kurti, Aishe and Jeevaratnam, Suren and Macyczko, Jesse R and Roy, Bhaskar and Izhar, Taha and Wang, Ni and others},
title = {{Amyloid pathology and cognitive impairment in hAβ-KI and APPSAA-KI mouse models of Alzheimer's disease}},
journal = {Neurobiology of aging},
year = {2025},
doi = {10.1016/j.neurobiolaging.2024.10.005},
pmid = {39447490},
url = {https://doi.org/10.1016/j.neurobiolaging.2024.10.005}
}
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Key findings
- Both APPSAA-KI and hAβ-KI mice exhibit cognitive impairments, wherein no significant differences are found between these two models, although APPSAA KI mice show a trend towards worse cognitive function.
- Notably, female hAβ-KI and APPSAA-KI mice have a more pronounced cognitive impairments compared to their respective males.
- Our findings suggest that Aβ humanization contributes to cognitive deficits in APPSAA-KI mice, and that amyloid deposition might not be closely associated with cognitive impairments in APPSAA-KI mice.
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Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomized / 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, multicenter collaboration and free to read, so those were left out: it earned 24 of the 56 points we could judge it on, which is 43 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| 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 | 4 / 5 | 2025 — within 3 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 “mouse”) — scores zero |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39447490) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 24 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 24 of the 56 points we could judge it on is 43 out of 100. |
| Total | 43 / 100 | — |
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