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Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform
Ishihara T, Hong M, Zhang B, Nakagawa Y, Lee MK, Trojanowski JQ, Lee VM.. Neuron, 1999-11-01
Topic: Brain proteins, microglia and lab models
Plain-language summary
Filamentous tau aggregates are hallmarks of tauopathies, e.g., frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) and amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC). Since FTDP-17 tau gene mutations alter levels/functions of tau, we overexpressed the smallest human tau isoform in the CNS of transgenic (Tg) mice to model tauopathies. These mice acquired age-dependent CNS pathology similarto FTDP-17 and ALS/PDC, including insoluble, hyperphosphorylated tau and argyrophilic intraneuronal inclusions formed by tau-immunoreactive filaments. Inclusions were present in cortical and brainstem neurons but were most abundant in spinal cord neurons, where they were associated with axon degeneration, diminished microtubules (MTs), and reduced axonal transport in ventral roots, as well as spinal cord gliosis and motor weakness. These Tg mice recapitulate key features of tauopathies and provide models for elucidating mechanisms underlying diverse tauopathies, including Alzheimer's disease (AD).
What this study adds
Evidence grade: Low
Transgenic mice overexpressing the smallest human tau isoform developed age-dependent tau pathology, including insoluble hyperphosphorylated tau and inclusions, with axon degeneration and motor weakness. This is an animal model for studying tauopathies, not a treatment or cure.
Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Ishihara, T., Hong, M., Zhang, B., Nakagawa, Y., Lee, M. K., Trojanowski, J. Q., et al. (1999). Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron. https://doi.org/10.1016/s0896-6273(00)81127-7
Vancouver
Ishihara T, Hong M, Zhang B, Nakagawa Y, Lee MK, Trojanowski JQ, et al. Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform. Neuron. 1999. doi:10.1016/s0896-6273(00)81127-7. PMID: 10595524.
BibTeX
@article{ishihara1999-10595524,
author = {Ishihara, T. and Hong, M. and Zhang, B. and Nakagawa, Y. and Lee, M. K. and Trojanowski, J. Q. and Lee, V. M.},
title = {{Age-dependent emergence and progression of a tauopathy in transgenic mice overexpressing the shortest human tau isoform}},
journal = {Neuron},
year = {1999},
doi = {10.1016/s0896-6273(00)81127-7},
pmid = {10595524},
url = {https://doi.org/10.1016/s0896-6273(00)81127-7}
}
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 7 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.
Key findings
- Inclusions were present in cortical and brainstem neurons but were most abundant in spinal cord neurons, where they were associated with axon degeneration, diminished microtubules (MTs), and reduced axonal transport in ventral roots, as well as spinal cord gliosis and motor weakness.
Why it matters
Transgenic mice overexpressing the smallest human tau isoform developed age-dependent tau pathology, including insoluble hyperphosphorylated tau and inclusions, with axon degeneration and motor weakness. This is an animal model for studying tauopathies, not a treatment or cure.
Study details
- Evidence strengthLow
How this study scored 50/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neuron) |
| Journal's citation record | 4 / 4 | Neuron: journal h-index 689 (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 | 1999 — older than 20 years, still counted |
| 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 |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 567 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.6 citations a year over 29 year(s) since 1999 |
| Impact for its field and year | 4 / 6 | Cited 17.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 16 other studies in this library |
| Still being cited | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Virginia M.‐Y. Lee: h-index 202 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 10595524) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 100 | — |
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