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The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome
Milenkovic I, Jarc J, Dassler E, Aronica E, Iyer A, Adle-Biassette H, Scharrer A, Reischer T et al.. Neuropathology and applied neurobiology, 2017-05-25
Topic: Brain proteins, microglia and lab models
Aims Down syndrome (DS) is a common cause of mental retardation accompanied by cognitive impairment. Comprehensive studies suggested a link between development and ageing, as nearly all individuals with DS develop Alzheimer disease (AD)-like pathology. However, there is still a paucity of data on tau in early DS to support this notion. Methods Using morphometric immunohistochemistry we compared tau phosphorylation in normal brains and in brains of individuals with DS from early development until early postnatal life. Results We observed in DS a critical loss of physiological phosphorylation of tau. Rhombencephalic structures showed prominent differences between controls and DS using antibodies AT8 (Ser-202/Thr-205) and AT180 (Thr-231). In contrast, in the subiculum only a small portion of controls deviated from DS using antibodies AT100 (Thr-212/Ser-214) and AT270 (Thr-181). With exception of the subiculum, phosphorylation-independent tau did not differ between groups, as confirmed by immunostaining for the HT-7 antibody (epitope between 159 and 163 of the human tau) as well. Discussion Our observations suggest functional tau disturbance in DS brains during development, rather than axonal loss. This supports the role of tau as a further important player in the pathophysiology of cognitive impairment in DS and related AD.
Key findings
- Results We observed in DS a critical loss of physiological phosphorylation of tau.
Why it matters
This brain tissue study found that the normal phosphorylation of the tau protein was critically changed in fetal Down syndrome brains, suggesting tau problems begin early in development. The findings are from tissue analysis and suggest tau may play a role in cognitive impairment in Down syndrome and related Alzheimer's disease, but no treatment was tested.
Study details
- Evidence strengthLow
How this study scored 38/100
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 (Neuropathology and applied neurobiology) |
| Journal's citation record | 1 / 4 | Neuropathology and Applied Neurobiology: journal h-index 143 (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 | 2018 — 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 | 3 / 7 | Cited 29 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.9 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 2 / 6 | Cited 1.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Gábor Géza Kovács: h-index 90 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Inserm: institution h-index 1,988 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 9 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28455903) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 38 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Milenkovic, I., Jarc, J., Dassler, E., Aronica, E., Iyer, A., Adle-Biassette, H., et al. (2018). The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome. Neuropathology and applied neurobiology. https://doi.org/10.1111/nan.12406
Vancouver
Milenkovic I, Jarc J, Dassler E, Aronica E, Iyer A, Adle-Biassette H, et al. The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome. Neuropathology and applied neurobiology. 2018. doi:10.1111/nan.12406. PMID: 28455903.
BibTeX
@article{milenkovic2018-28455903,
author = {Milenkovic, I. and Jarc, J. and Dassler, E. and Aronica, E. and Iyer, A. and Adle-Biassette, H. and Scharrer, A. and Reischer, T. and others},
title = {{The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome}},
journal = {Neuropathology and applied neurobiology},
year = {2018},
doi = {10.1111/nan.12406},
pmid = {28455903},
url = {https://doi.org/10.1111/nan.12406}
}
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