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Genetic targeting aromatase in male amyloid precursor protein transgenic mice down-regulates beta-secretase (BACE1) and prevents Alzheimer-like pathology and cognitive impairment
McAllister C, Long J, Bowers A, Walker A, Cao P, Honda S, Harada N, Staufenbiel M et al.. The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010-05-01
Topic: Brain proteins, microglia and lab models
As brain testosterone plays both androgenic and estrogenic actions due to its conversion into estrogen via aromatase naturally, it is unclear that the age-related reduction of testosterone increased risk of Alzheimer's disease (AD) in men is mediated through androgen alone or both androgen and estrogen mechanisms. Our previous studies using a gene-based approach in mouse model to block the conversion of testosterone into estrogen (aromatase gene knock-out, ArKO), found a depletion of estrogen and increase in testosterone endogenously in males. Here, we use crossing the ArKO mice with APP23 transgenic mice, a mouse model of AD, to produce APP23/Ar(+/-) mice to study the estrogen-independent effect of testosterone on AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
McAllister, C., Long, J., Bowers, A., Walker, A., Cao, P., Honda, S., et al. (2010). Genetic targeting aromatase in male amyloid precursor protein transgenic mice down-regulates beta-secretase (BACE1) and prevents Alzheimer-like pathology and cognitive impairment. The Journal of neuroscience : the official journal of the Society for Neuroscience. https://doi.org/10.1523/jneurosci.1180-10.2010
Vancouver
McAllister C, Long J, Bowers A, Walker A, Cao P, Honda S, et al. Genetic targeting aromatase in male amyloid precursor protein transgenic mice down-regulates beta-secretase (BACE1) and prevents Alzheimer-like pathology and cognitive impairment. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2010. doi:10.1523/jneurosci.1180-10.2010. PMID: 20505099.
BibTeX
@article{mcallister2010-20505099,
author = {McAllister, C. and Long, J. and Bowers, A. and Walker, A. and Cao, P. and Honda, S. and Harada, N. and Staufenbiel, M. and others},
title = {{Genetic targeting aromatase in male amyloid precursor protein transgenic mice down-regulates beta-secretase (BACE1) and prevents Alzheimer-like pathology and cognitive impairment}},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
year = {2010},
doi = {10.1523/jneurosci.1180-10.2010},
pmid = {20505099},
url = {https://doi.org/10.1523/jneurosci.1180-10.2010}
}
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Our previous studies using a gene-based approach in mouse model to block the conversion of testosterone into estrogen (aromatase gene knock-out, ArKO), found a depletion of estrogen and increase in testosterone endogenously in males.
- Here, we use crossing the ArKO mice with APP23 transgenic mice, a mouse model of AD, to produce APP23/Ar(+/-) mice to study the estrogen-independent effect of testosterone on AD.
- We found a significant reduction in brain plaque formation, improved cognitive function and increase NEP activity in male APP23/Ar(+/-) mice compared with age-matched male APP23 controls.
- In addition, we found, for the first time, a reduction of beta-secretase (BACE1) enzyme activity, mRNA level and protein expression in the male APP23/Ar(+/-) mice, suggesting that endogenous testosterone, independent from estrogen, may protect against AD in males via two major mechanisms, downregulation of BACE1 activities at transcriptional level to reduce beta amyloid production and upregulation of NEP activities to enhance bate amyloid degradation.
Why it matters
In a mouse model of Alzheimer's disease, blocking the conversion of testosterone into estrogen reduced brain plaques and improved cognitive function. These are animal results, so it is not yet known whether the same approach would work or be safe in people.
New to this subject? Start with our plain-English guide: Genetics →
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The Journal of neuroscience : the official journal of the Society for Neuroscience) |
| Journal's citation record | 4 / 4 | Journal of Neuroscience: journal h-index 651 (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 | 1 / 5 | 2010 — 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 “transgenic”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 101 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.6 citations a year over 18 year(s) since 2010 |
| Impact for its field and year | 3 / 6 | Cited 3.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Rena Li: h-index 35 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Novartis (Switzerland): institution h-index 638 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20505099) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 41 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1523/jneurosci.1180-10.2010
- PubMed: 20505099
- Original source →
- Free full text: Journal of Neuroscience →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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