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Frameshift proteins in autosomal dominant forms of Alzheimer disease and other tauopathies
van Leeuwen FW, van Tijn P, Sonnemans MA, Hobo B, Mann DM, Van Broeckhoven C, Kumar-Singh S, Cras P et al.. Neurology, 2006-01-01
Topic: Brain proteins, microglia and lab models
Frameshift (+1) proteins such as APP(+1) and UBB(+1) accumulate in sporadic cases of Alzheimer disease (AD) and in older subjects with Down syndrome (DS). We investigated whether these proteins also accumulate at an early stage of neuropathogenesis in young DS individuals without neuropathology and in early-onset familial forms of AD (FAD), as well as in other tauopathies, such as Pick disease (PiD) or progressive supranuclear palsy (PSP). APP(+1) is present in many neurons and beaded neurites in very young cases of DS, which suggests that it is axonally transported. In older DS patients (>37 years), a mixed pattern of APP(+1) immunoreactivity was observed in healthy looking neurons and neurites, dystrophic neurites, in association with neuritic plaques, as well as neurofibrillary tangles. UBB(+1) immunoreactivity was exclusively present in AD type of neuropathology. A similar pattern of APP(+1) and UBB(+1) immunoreactivity was also observed for FAD and much less explicit in nondemented controls after the age of 51 years. Furthermore, we observed accumulation of +1 proteins in other types of tauopathies, such as PiD, frontotemporal dementia, PSP and argyrophylic grain disease. These data suggest that accumulation of +1 proteins contributes to the early stages of dementia and plays a pathogenic role in a number of diseases that involve the accumulation of tau.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
van Leeuwen, F. W., van Tijn, P., Sonnemans, M. A., Hobo, B., Mann, D. M., Van Broeckhoven, C., et al. (2006). Frameshift proteins in autosomal dominant forms of Alzheimer disease and other tauopathies. Neurology. https://doi.org/10.1212/01.wnl.0000193882.46003.6d
Vancouver
van Leeuwen FW, van Tijn P, Sonnemans MA, Hobo B, Mann DM, Van Broeckhoven C, et al. Frameshift proteins in autosomal dominant forms of Alzheimer disease and other tauopathies. Neurology. 2006. doi:10.1212/01.wnl.0000193882.46003.6d. PMID: 16432153.
BibTeX
@article{vanleeuwen2006-16432153,
author = {van Leeuwen, F. W. and van Tijn, P. and Sonnemans, M. A. and Hobo, B. and Mann, D. M. and Van Broeckhoven, C. and Kumar-Singh, S. and Cras, P. and others},
title = {{Frameshift proteins in autosomal dominant forms of Alzheimer disease and other tauopathies}},
journal = {Neurology},
year = {2006},
doi = {10.1212/01.wnl.0000193882.46003.6d},
pmid = {16432153},
url = {https://doi.org/10.1212/01.wnl.0000193882.46003.6d}
}
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Key findings
- APP(+1) is present in many neurons and beaded neurites in very young cases of DS, which suggests that it is axonally transported.
- Furthermore, we observed accumulation of +1 proteins in other types of tauopathies, such as PiD, frontotemporal dementia, PSP and argyrophylic grain disease.
- These data suggest that accumulation of +1 proteins contributes to the early stages of dementia and plays a pathogenic role in a number of diseases that involve the accumulation of tau.
Why it matters
This study found that frameshift proteins accumulate early in young people with Down syndrome and in familial Alzheimer disease, and also in other tauopathies. It suggests these proteins contribute to early dementia, but it does not test any treatment or prevention.
Study details
- Evidence strengthLow
How this study scored 39/100
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 (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 2006 — 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 | 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 42 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.9 citations a year over 22 year(s) since 2006 |
| Impact for its field and year | 2 / 6 | Cited 2.7× 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 | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author David F. Fischer: h-index 38 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Manchester: institution h-index 1,304 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 16432153) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 39 / 100 | — |
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