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Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype
Blom ES, Giedraitis V, Zetterberg H, Fukumoto H, Blennow K, Hyman BT, Irizarry MC, Wahlund LO et al.. Dementia and geriatric cognitive disorders, 2009-05-07
Topic: Amyloid, tau and blood-test diagnosis
Background/aims Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-beta42 (Abeta42) and the apolipoprotein E gene (APOE) epsilon4 allele predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Here, we investigated these markers to assess their predictive value and influence on the rate of disease progression. Methods Using ELISA, we measured the CSF biomarkers in 47 AD patients, 58 patients with MCI and 35 healthy control subjects. Twenty-eight MCI patients revisited the clinic and half of them progressed to AD during a period of 3-12 years. Results The expected changes in CSF total (T)-tau, phosphorylated (P)-tau and Abeta42 levels were found in AD, confirming the diagnostic value of these biomarkers. We were also able to corroborate an increased risk for progression from MCI to AD with elevated CSF T-tau and P-tau and with the presence of the APOE epsilon4/epsilon4 genotype, but not with decreased Abeta42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE epsilon4 homozygosity progressed faster from MCI to AD. Conclusions CSF T-tau and P-tau as well as the APOE epsilon4/epsilon4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD.
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APA 7th
Blom, E. S., Giedraitis, V., Zetterberg, H., Fukumoto, H., Blennow, K., Hyman, B. T., et al. (2009). Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype. Dementia and geriatric cognitive disorders. https://doi.org/10.1159/000216841
Vancouver
Blom ES, Giedraitis V, Zetterberg H, Fukumoto H, Blennow K, Hyman BT, et al. Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype. Dementia and geriatric cognitive disorders. 2009. doi:10.1159/000216841. PMID: 19420940.
BibTeX
@article{blom2009-19420940,
author = {Blom, E. S. and Giedraitis, V. and Zetterberg, H. and Fukumoto, H. and Blennow, K. and Hyman, B. T. and Irizarry, M. C. and Wahlund, L. O. and others},
title = {{Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype}},
journal = {Dementia and geriatric cognitive disorders},
year = {2009},
doi = {10.1159/000216841},
pmid = {19420940},
url = {https://doi.org/10.1159/000216841}
}
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
- Results The expected changes in CSF total (T)-tau, phosphorylated (P)-tau and Abeta42 levels were found in AD, confirming the diagnostic value of these biomarkers.
- We were also able to corroborate an increased risk for progression from MCI to AD with elevated CSF T-tau and P-tau and with the presence of the APOE epsilon4/epsilon4 genotype, but not with decreased Abeta42.
- Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE epsilon4 homozygosity progressed faster from MCI to AD.
- Conclusions CSF T-tau and P-tau as well as the APOE epsilon4/epsilon4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD.
Why it matters
In this study of 47 Alzheimer's, 58 mild cognitive impairment and 35 control participants, high CSF total tau or phosphorylated tau together with the APOE epsilon4/epsilon4 genotype predicted faster progression from mild cognitive impairment to Alzheimer's. It is about predicting progression, not about treating, curing or preventing the disease.
Study details
- Participants58
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Dementia and geriatric cognitive disorders) |
| Journal's citation record | 1 / 4 | Dementia and Geriatric Cognitive Disorders: journal h-index 149 (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 | 2009 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 58 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 140 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.4 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 3 / 6 | Cited 7.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 1 / 4 | Cited 14 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Martin Ingelsson: h-index 75 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Massachusetts General Hospital: institution h-index 2,057 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19420940) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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