Apolipoprotein E genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease
Lautner R, Palmqvist S, Mattsson N, Andreasson U, Wallin A, Pålsson E, Jakobsson J, Herukka SK et al.. JAMA psychiatry, 2014-10-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Several studies suggest that the apolipoprotein E (APOE) ε4 allele modulates cerebrospinal fluid (CSF) levels of β-amyloid 42 (Aβ42). Whether this effect is secondary to the association of the APOE ε4 allele with cortical Aβ deposition or whether APOE ε4 directly influences CSF levels of Aβ42 independently of Aβ pathology remains unknown. Objective To evaluate whether the APOE genotype affects the diagnostic accuracy of CSF biomarkers for Alzheimer disease (AD), in particular Aβ42 levels, and whether the association of APOE ε4 with CSF biomarkers depends on cortical Aβ status. Design, setting, and participants We collected data from 4 different centers in Sweden, Finland, and Germany. Cohort A consisted of 1345 individuals aged 23 to 99 years with baseline CSF samples, including 309 with AD, 287 with prodromal AD, 399 with stable mild cognitive impairment, 99 with dementias other than AD, and 251 controls. Cohort B included 105 nondemented younger individuals (aged 20-34 years) with CSF samples available. Cohort C included 118 patients aged 60 to 80 years with mild cognitive symptoms who underwent flutemetamol F 18 ([18F]flumetamol) positron emission tomography amyloid imaging and CSF tap. Exposures Standard care. Main outcomes and measures Cerebrospinal fluid levels of Aβ42 and total and phosphorylated tau in relation to the APOE ε2/ε3/ε4 polymorphism in different diagnostic groups and in cases with or without cortical uptake of [18F]flutemetamol. Results The CSF levels of Aβ42 but not total and phosphorylated tau were lower in APOE ε4 carriers compared with noncarriers irrespective of diagnostic group (cohort A). Despite this, CSF levels of Aβ42 differed between participants with AD when compared with controls and those with stable mild cognitive impairment, even when stratifying for APOE genotype (P Conclusions and relevance Cerebrospinal fluid levels of Aβ42 are strongly associated with the diagnosis of AD and cortical Aβ accumulation independent of APOE genotype. The clinical cutoff for CSF levels of Aβ42 should be the same for all APOE genotypes.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Lautner, R., Palmqvist, S., Mattsson, N., Andreasson, U., Wallin, A., Pålsson, E., et al. (2014). Apolipoprotein E genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease. JAMA psychiatry. https://doi.org/10.1001/jamapsychiatry.2014.1060
Vancouver
Lautner R, Palmqvist S, Mattsson N, Andreasson U, Wallin A, Pålsson E, et al. Apolipoprotein E genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease. JAMA psychiatry. 2014. doi:10.1001/jamapsychiatry.2014.1060. PMID: 25162367.
BibTeX
@article{lautner2014-25162367,
author = {Lautner, R. and Palmqvist, S. and Mattsson, N. and Andreasson, U. and Wallin, A. and Pålsson, E. and Jakobsson, J. and Herukka, S. K. and others},
title = {{Apolipoprotein E genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease}},
journal = {JAMA psychiatry},
year = {2014},
doi = {10.1001/jamapsychiatry.2014.1060},
pmid = {25162367},
url = {https://doi.org/10.1001/jamapsychiatry.2014.1060}
}
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
- Importance Several studies suggest that the apolipoprotein E (APOE) ε4 allele modulates cerebrospinal fluid (CSF) levels of β-amyloid 42 (Aβ42).
- Results The CSF levels of Aβ42 but not total and phosphorylated tau were lower in APOE ε4 carriers compared with noncarriers irrespective of diagnostic group (cohort A).
- Despite this, CSF levels of Aβ42 differed between participants with AD when compared with controls and those with stable mild cognitive impairment, even when stratifying for APOE genotype (P < .001 to P = .006).
Why it matters
This study found that CSF levels of Aβ42 were lower in APOE ε4 carriers regardless of diagnostic group, but Aβ42 still differed between Alzheimer disease and controls even when stratifying by APOE genotype. It concerns the accuracy of CSF biomarkers for diagnosis, not treatment, cure, or prevention.
New to this subject? Start with our plain-English guide: Genetics →
Study details
- Participants105
- Evidence strengthModerate
How this study scored 57/100
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 (JAMA psychiatry) |
| Journal's citation record | 3 / 4 | JAMA Psychiatry: journal h-index 256 (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 | 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 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 105 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 107 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.6 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 4 / 6 | Cited 9.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 2 / 4 | Cited 15 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Oskar Hansson: h-index 148 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 10 institution(s) in 6 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25162367) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamapsychiatry.2014.1060
- PubMed: 25162367
- Original source →
- Free full text: jamanetwork.com →
Full text: free to read — Unpaywall lists this copy as free to read: the link above (checked 10 Oct 2026).
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 21.
Later studies that cite this one
9 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Genetics
Also tagged “cerebrospinal”
821 studies in the library carry the topic tag “cerebrospinal”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 821 tagged studies.