CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings
Seppälä TT, Nerg O, Koivisto AM, Rummukainen J, Puli L, Zetterberg H, Pyykkö OT, Helisalmi S et al.. Neurology, 2012-04-18
Topic: Amyloid, tau and blood-test diagnosis
Objective To assess the relationship between Alzheimer disease (AD)-related pathologic changes in frontal cortical brain biopsy and AD biomarkers in ventricular vs lumbar CSF, and to evaluate the relationships of AD biomarkers in CSF and cortical biopsy with the final clinical diagnosis of AD. Methods In 182 patients with presumed normal pressure hydrocephalus (152 with known APOE carrier status), Aβ plaques and tau in the cortical brain biopsies were correlated with the ventricular and lumbar CSF Aβ42, total tau, and p-tau levels measured by ELISA. In a median follow-up of 2.0 years, 51 patients developed AD dementia. Results The patients with Aβ plaques in the cortical biopsy had lower (p = 0.009) CSF Aβ42 levels than those with no Aβ plaques. The patients with tau in the cortical biopsy had lower (p = 0.014) Aβ42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy. The patients with amyloid + tau + biopsies had the lowest Aβ42 and highest tau and p-tau 181 levels in CSF. The Aβ42 levels were lower and the tau and p-tau 181 higher in the ventricular vs corresponding lumbar CSF samples. In multivariate analysis, the presence of cortical Aβ was independently predicted by the APOE ε4 carrier status and age but not by CSF Aβ42 or tau levels. Conclusions Amyloid plaques and hyperphosphorylated tau in cortical brain biopsies are reflected by low CSF Aβ42 and high CSF tau and p-tau levels, respectively.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Seppälä, T. T., Nerg, O., Koivisto, A. M., Rummukainen, J., Puli, L., Zetterberg, H., et al. (2012). CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings. Neurology. https://doi.org/10.1212/wnl.0b013e3182563bd0
Vancouver
Seppälä TT, Nerg O, Koivisto AM, Rummukainen J, Puli L, Zetterberg H, et al. CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings. Neurology. 2012. doi:10.1212/wnl.0b013e3182563bd0. PMID: 22517093.
BibTeX
@article{seppala2012-22517093,
author = {Seppälä, T. T. and Nerg, O. and Koivisto, A. M. and Rummukainen, J. and Puli, L. and Zetterberg, H. and Pyykkö, O. T. and Helisalmi, S. and others},
title = {{CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings}},
journal = {Neurology},
year = {2012},
doi = {10.1212/wnl.0b013e3182563bd0},
pmid = {22517093},
url = {https://doi.org/10.1212/wnl.0b013e3182563bd0}
}
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Key findings
- Results The patients with Aβ plaques in the cortical biopsy had lower (p = 0.009) CSF Aβ42 levels than those with no Aβ plaques.
- The patients with tau in the cortical biopsy had lower (p = 0.014) Aβ42 but higher (p = 0.015) p-tau 181 in CSF as compared to those with no tau in the cortical biopsy.
Why it matters
In patients who had brain biopsies, those with amyloid plaques or tau in the tissue tended to have lower Aβ42 and higher tau and p-tau 181 in their spinal fluid. This supports using spinal fluid markers to reflect brain changes, which aids diagnosis but does not treat or prevent the disease.
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Study details
- Participants182
- Evidence strengthLow
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / 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 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 182 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 239 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.9 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 4 / 6 | Cited 14.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 16 other studies in this library |
| Still being cited | 2 / 4 | Cited 23 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Sanna‐Kaisa Herukka: h-index 52 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | University of Eastern Finland: institution h-index 616 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22517093) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 52 / 100 | — |
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