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Ordered Assembly of Tau Protein and Neurodegeneration
Goedert M, Spillantini MG.. Advances in experimental medicine and biology, 2019-01-01
Topic: Brain proteins, microglia and lab models
Tau filaments with distinct morphologies and/or isoform compositions underlie a large number of human neurodegenerative diseases. Their formation is important, because dominantly inherited mutations in MAPT, the tau gene, cause frontotemporal dementia with abundant filamentous tau inclusions. Assembly of tau may begin in a specific region of the brain, from where it spreads to other areas. It remains to be seen if the molecular species underlying tau aggregate-mediated neurodegeneration and propagation are the same or different. In the brains of mice transgenic for human mutant P301S tau, small tau filaments are the predominant seed-competent species. It has been suggested that different conformers of assembled tau may give rise to different human tauopathies, but until recently, it was not possible to study this directly. Electron cryo-microscopy can now be used to determine high-resolution structures of amyloid filaments from human brain. Paired helical and straight tau filaments of Alzheimer's disease are ultrastructural polymorphs. Each filament core is composed of two identical protofilaments extending from G273/304-E380 (in the numbering of the 441 amino acid isoform of human tau), which adopt a combined cross-β/β-helix structure. They comprise the ends of the first or second microtubule-binding repeat (R1 or R2), the whole of R3 and R4, as well as 12 amino acids after R4. By contrast, the core of the narrow filament of Pick's disease consists of a single protofilament extending from K254-F378 of 3R tau, which adopts a cross-β structure. It comprises the last 21 amino acids of R1, all of R3 and R4, as well as 10 amino acids after R4. Wide tau filaments of Pick's disease, which are in the minority, consist of two narrow filaments packed against each other. The tau filament folds of Alzheimer's and Pick's diseases appear to be conserved between different cases of disease. These findings show that filamentous tau adopts one fold in Alzheimer's disease and a different fold in Pick's disease, establishing the existence of distinct conformers.
Key findings
- It has been suggested that different conformers of assembled tau may give rise to different human tauopathies, but until recently, it was not possible to study this directly.
- These findings show that filamentous tau adopts one fold in Alzheimer's disease and a different fold in Pick's disease, establishing the existence of distinct conformers.
Why it matters
This work describes the ordered assembly of tau protein and reports that tau filaments adopt one fold in Alzheimer's disease and a different fold in Pick's disease, establishing distinct conformers. It is basic structural research and does not report a treatment, cure, or prevention for Alzheimer's disease.
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Study details
- Evidence strengthLow
How this study scored 44/100
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. We have no data on journal's citation record, so that was left out: it earned 42 of the 96 points we could judge it on, which is 44 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Advances in experimental medicine and biology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2019 — 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 | 4 / 7 | Cited 72 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.0 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 5 / 6 | Cited 27.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 31 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Maria Grazia Spillantini: h-index 92 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 32096024) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 42 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 42 of the 96 points we could judge it on is 44 out of 100. |
| Total | 44 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Goedert, M., & Spillantini, M. G. (2019). Ordered Assembly of Tau Protein and Neurodegeneration. Advances in experimental medicine and biology. https://doi.org/10.1007/978-981-32-9358-8_1
Vancouver
Goedert M, Spillantini MG. Ordered Assembly of Tau Protein and Neurodegeneration. Advances in experimental medicine and biology. 2019. doi:10.1007/978-981-32-9358-8_1. PMID: 32096024.
BibTeX
@article{goedert2019-32096024,
author = {Goedert, M. and Spillantini, M. G.},
title = {{Ordered Assembly of Tau Protein and Neurodegeneration}},
journal = {Advances in experimental medicine and biology},
year = {2019},
doi = {10.1007/978-981-32-9358-8_1},
pmid = {32096024},
url = {https://doi.org/10.1007/978-981-32-9358-8_1}
}
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