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Leveraging preclinical models for the development of Alzheimer disease therapeutics
Scearce-Levie K, Sanchez PE, Lewcock JW.. Nature reviews. Drug discovery, 2020-04-08
Topic: Amyloid, tau and blood-test diagnosis
A large number of mouse models have been engineered, characterized and used to advance biomedical research in Alzheimer disease (AD). Early models simply damaged the rodent brain through toxins or lesions. Later, the spread of genetic engineering technology enabled investigators to develop models of familial AD by overexpressing human genes such as those encoding amyloid precursor protein (APP) or presenilins (PSEN1 or PSEN2) carrying mutations linked to early-onset AD.
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APA 7th
Scearce-Levie, K., Sanchez, P. E., & Lewcock, J. W. (2020). Leveraging preclinical models for the development of Alzheimer disease therapeutics. Nature reviews. Drug discovery. https://doi.org/10.1038/s41573-020-0065-9
Vancouver
Scearce-Levie K, Sanchez PE, Lewcock JW. Leveraging preclinical models for the development of Alzheimer disease therapeutics. Nature reviews. Drug discovery. 2020. doi:10.1038/s41573-020-0065-9. PMID: 32612262.
BibTeX
@article{scearcelevie2020-32612262,
author = {Scearce-Levie, K. and Sanchez, P. E. and Lewcock, J. W.},
title = {{Leveraging preclinical models for the development of Alzheimer disease therapeutics}},
journal = {Nature reviews. Drug discovery},
year = {2020},
doi = {10.1038/s41573-020-0065-9},
pmid = {32612262},
url = {https://doi.org/10.1038/s41573-020-0065-9}
}
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Key findings
- Early models simply damaged the rodent brain through toxins or lesions.
- Later, the spread of genetic engineering technology enabled investigators to develop models of familial AD by overexpressing human genes such as those encoding amyloid precursor protein (APP) or presenilins (PSEN1 or PSEN2) carrying mutations linked to early-onset AD.
- Recently, more complex models have sought to explore the impact of multiple genetic risk factors in the context of different biological challenges.
- Although none of these models has proven to be a fully faithful reproduction of the human disease, models remain essential as tools to improve our understanding of AD biology, conduct thorough pharmacokinetic and pharmacodynamic analyses, discover translatable biomarkers and evaluate specific therapeutic approaches.
Why it matters
This review discusses how preclinical mouse models have been engineered and used to advance Alzheimer disease research, from early toxin or lesion models to genetic models of familial disease. It describes research tools and does not report a treatment, cure or prevention for patients.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Evidence strengthLow
How this study scored 42/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Nature reviews. Drug discovery) |
| Journal's citation record | 3 / 4 | Nature Reviews Drug Discovery: journal h-index 479 (OpenAlex, 2026-10-29) |
| 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 | 2020 — 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 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 120 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 15.0 citations a year over 8 year(s) since 2020 |
| Impact for its field and year | 3 / 6 | Cited 3.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 2 / 4 | Cited 45 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Joseph W. Lewcock: h-index 39 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Denali Therapeutics (United States): institution h-index 217 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32612262) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 42 / 100 | — |
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