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Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network
Takahashi H, Klein ZA, Bhagat SM, Kaufman AC, Kostylev MA, Ikezu T, Strittmatter SM, Alzheimer’s Disease Neuroimaging Initiative.. Acta neuropathologica, 2017-01-09
Topic: Brain proteins, microglia and lab models
Plain-language summary
Progranulin (PGRN) is implicated in Alzheimer's disease (AD) as well as frontotemporal lobar degeneration. Genetic studies demonstrate an association of the common GRN rs5848 variant that results in reduced PGRN levels with increased risk for AD. However, the mechanisms by which PGRN reduction from the GRN AD risk variant or mutation exacerbates AD pathophysiology remain ill defined.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Takahashi, H., Klein, Z. A., Bhagat, S. M., Kaufman, A. C., Kostylev, M. A., Ikezu, T., et al. (2017). Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network. Acta neuropathologica. https://doi.org/10.1007/s00401-017-1668-z
Vancouver
Takahashi H, Klein ZA, Bhagat SM, Kaufman AC, Kostylev MA, Ikezu T, et al. Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network. Acta neuropathologica. 2017. doi:10.1007/s00401-017-1668-z. PMID: 28070672.
BibTeX
@article{takahashi2017-28070672,
author = {Takahashi, H. and Klein, Z. A. and Bhagat, S. M. and Kaufman, A. C. and Kostylev, M. A. and Ikezu, T. and Strittmatter, S. M. and {Alzheimer’s Disease Neuroimaging Initiative}},
title = {{Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network}},
journal = {Acta neuropathologica},
year = {2017},
doi = {10.1007/s00401-017-1668-z},
pmid = {28070672},
url = {https://doi.org/10.1007/s00401-017-1668-z}
}
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 8 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
- Genetic studies demonstrate an association of the common GRN rs5848 variant that results in reduced PGRN levels with increased risk for AD.
- However, the mechanisms by which PGRN reduction from the GRN AD risk variant or mutation exacerbates AD pathophysiology remain ill defined.
- Here, we show that the GRN AD risk variant has no significant effects on florbetapir positron emission tomographic amyloid imaging and cerebrospinal fluid (CSF) Aβ levels, whereas it is associated with increased CSF tau levels in human subjects of the Alzheimer's disease neuroimaging initiative studies.
- Consistent with the human data, subsequent analyses using the APPswe/PS1ΔE9 (APP/PS1) mouse model of cerebral amyloidosis show that PGRN deficiency has no exacerbating effects on Aβ pathology.
Why it matters
This study found that the GRN Alzheimer's disease risk variant had no significant effects on amyloid imaging or cerebrospinal fluid Aβ levels, whereas it was associated with increased cerebrospinal fluid tau. It is an observational genetic and biomarker analysis and does not report any treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Acta neuropathologica) |
| Journal's citation record | 3 / 4 | Acta Neuropathologica: journal h-index 287 (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 | 2017 — 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 84 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.6 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 3 / 6 | Cited 6.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 2 / 4 | Cited 22 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Stephen M. Strittmatter: h-index 104 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Yale University: institution h-index 1,927 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28070672) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
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