SNPs associated with cerebrospinal fluid phospho-tau levels influence rate of decline in Alzheimer's disease
Cruchaga C, Kauwe JS, Mayo K, Spiegel N, Bertelsen S, Nowotny P, Shah AR, Abraham R et al.. PLoS genetics, 2010-09-16
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's Disease (AD) is a complex and multifactorial disease. While large genome-wide association studies have had some success in identifying novel genetic risk factors for AD, case-control studies are less likely to uncover genetic factors that influence progression of disease. An alternative approach to identifying genetic risk for AD is the use of quantitative traits or endophenotypes. The use of endophenotypes has proven to be an effective strategy, implicating genetic risk factors in several diseases, including anemia, osteoporosis and heart disease. In this study we identify a genetic factor associated with the rate of decline in AD patients and present a methodology for identification of other such factors. We have used an established biomarker for AD, cerebrospinal fluid (CSF) tau phosphorylated at threonine 181 (ptau(181)) levels as an endophenotype for AD, identifying a SNP, rs1868402, in the gene encoding the regulatory sub-unit of protein phosphatase B, associated with CSF ptau(181) levels in two independent CSF series (P(combined) = 1.17 x 10(-05)). We show no association of rs1868402 with risk for AD or age at onset, but detected a very significant association with rate of progression of disease that is consistent in two independent series (P(combined) = 1.17 x 10(-05)). Our analyses suggest that genetic variants associated with CSF ptau(181) levels may have a greater impact on rate of progression, while genetic variants such as APOE4, that are associated with CSF Aβ(42) levels influence risk and onset but not the rate of progression. Our results also suggest that drugs that inhibit or decrease tau phosphorylation may slow cognitive decline in individuals with very mild dementia or delay the appearance of memory problems in elderly individuals with low CSF Aβ(42) levels. Finally, we believe genome-wide association studies of CSF tau/ptau(181) levels should identify novel genetic variants which will likely influence rate of progression of AD.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Cruchaga, C., Kauwe, J. S., Mayo, K., Spiegel, N., Bertelsen, S., Nowotny, P., et al. (2010). SNPs associated with cerebrospinal fluid phospho-tau levels influence rate of decline in Alzheimer's disease. PLoS genetics. https://doi.org/10.1371/journal.pgen.1001101
Vancouver
Cruchaga C, Kauwe JS, Mayo K, Spiegel N, Bertelsen S, Nowotny P, et al. SNPs associated with cerebrospinal fluid phospho-tau levels influence rate of decline in Alzheimer's disease. PLoS genetics. 2010. doi:10.1371/journal.pgen.1001101. PMID: 20862329.
BibTeX
@article{cruchaga2010-20862329,
author = {Cruchaga, C. and Kauwe, J. S. and Mayo, K. and Spiegel, N. and Bertelsen, S. and Nowotny, P. and Shah, A. R. and Abraham, R. and others},
title = {{SNPs associated with cerebrospinal fluid phospho-tau levels influence rate of decline in Alzheimer's disease}},
journal = {PLoS genetics},
year = {2010},
doi = {10.1371/journal.pgen.1001101},
pmid = {20862329},
url = {https://doi.org/10.1371/journal.pgen.1001101}
}
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- In this study we identify a genetic factor associated with the rate of decline in AD patients and present a methodology for identification of other such factors.
- We have used an established biomarker for AD, cerebrospinal fluid (CSF) tau phosphorylated at threonine 181 (ptau(181)) levels as an endophenotype for AD, identifying a SNP, rs1868402, in the gene encoding the regulatory sub-unit of protein phosphatase B, associated with CSF ptau(181) levels in two independent CSF series (P(combined) = 1.17 x 10(-05)).
- We show no association of rs1868402 with risk for AD or age at onset, but detected a very significant association with rate of progression of disease that is consistent in two independent series (P(combined) = 1.17 x 10(-05)).
- Our analyses suggest that genetic variants associated with CSF ptau(181) levels may have a greater impact on rate of progression, while genetic variants such as APOE4, that are associated with CSF Aβ(42) levels influence risk and onset but not the rate of progression.
- Our results also suggest that drugs that inhibit or decrease tau phosphorylation may slow cognitive decline in individuals with very mild dementia or delay the appearance of memory problems in elderly individuals with low CSF Aβ(42) levels.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Study designcase-control study
- Evidence strengthModerate
How this study scored 53/100
Published in a peer-reviewed journal, and it is a case-control study. Scored zero for 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, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 31 of the 58 points we could judge it on, which is 53 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PLoS genetics) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 6 / 12 | A case-control study |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2010 — within 20 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 | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 20862329) |
| Free to read | 2 / 2 | Free to read |
| Points | 31 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 31 of the 58 points we could judge it on is 53 out of 100. |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Related studies in Genetics
Also tagged “phospho-tau”
4 studies in the library carry the topic tag “phospho-tau”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 4 tagged studies.