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Cerebrospinal fluid β-amyloid and phospho-tau biomarker interactions affecting brain structure in preclinical Alzheimer disease
Fortea J, Vilaplana E, Alcolea D, Carmona-Iragui M, Sánchez-Saudinos MB, Sala I, Antón-Aguirre S, González S et al.. Annals of neurology, 2014-06-13
Topic: Amyloid, tau and blood-test diagnosis
Objective To assess the relationships between core cerebrospinal fluid (CSF) biomarkers and cortical thickness (CTh) in preclinical Alzheimer disease (AD). Methods In this cross-sectional study, normal controls (n = 145) from the Alzheimer's Disease Neuroimaging Initiative underwent structural 3T magnetic resonance imaging (MRI) and lumbar puncture. CSF β-amyloid1-42 (Aβ) and phospho-tau₁₈₁p (p-tau) levels were measured by Luminex assays. Samples were dichotomized using published cutoffs (Aβ(+) /Aβ(-) and p-tau(+) /ptau(-)). CTh was measured by Freesurfer. CTh difference maps were derived from interaction and correlation analyses. Clusters from the interaction analysis were isolated to analyze the directionality of the interaction by analysis of covariance. Results We found a significant biomarker interaction between CSF Aβ and CSF p-tau levels affecting brain structure. Cortical atrophy only occurs in subjects with both Aβ(+) and p-tau(+). The stratified correlation analyses showed that the relationship between p-tau and CTh is modified by Aβ status and the relationship between Aβ and CTh is modified by p-tau status. p-Tau-dependent thinning was found in different cortical regions in Aβ(+) subjects but not in Aβ(-) subjects. Cortical thickening was related to decreasing CSF Aβ values in the absence of abnormal p-tau, but no correlations were found in p-tau(+) subjects. Interpretation Our data suggest that interactions between biomarkers in AD result in a 2-phase phenomenon of pathological cortical thickening associated with low CSF Aβ, followed by atrophy once CSF p-tau becomes abnormal. These interactions should be considered in clinical trials in preclinical AD, both when selecting patients and when using MRI as a surrogate marker of efficacy.
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APA 7th
Fortea, J., Vilaplana, E., Alcolea, D., Carmona-Iragui, M., Sánchez-Saudinos, M. B., Sala, I., et al. (2014). Cerebrospinal fluid β-amyloid and phospho-tau biomarker interactions affecting brain structure in preclinical Alzheimer disease. Annals of neurology. https://doi.org/10.1002/ana.24186
Vancouver
Fortea J, Vilaplana E, Alcolea D, Carmona-Iragui M, Sánchez-Saudinos MB, Sala I, et al. Cerebrospinal fluid β-amyloid and phospho-tau biomarker interactions affecting brain structure in preclinical Alzheimer disease. Annals of neurology. 2014. doi:10.1002/ana.24186. PMID: 24852682.
BibTeX
@article{fortea2014-24852682,
author = {Fortea, J. and Vilaplana, E. and Alcolea, D. and Carmona-Iragui, M. and Sánchez-Saudinos, M. B. and Sala, I. and Antón-Aguirre, S. and González, S. and others},
title = {{Cerebrospinal fluid β-amyloid and phospho-tau biomarker interactions affecting brain structure in preclinical Alzheimer disease}},
journal = {Annals of neurology},
year = {2014},
doi = {10.1002/ana.24186},
pmid = {24852682},
url = {https://doi.org/10.1002/ana.24186}
}
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Key findings
- Results We found a significant biomarker interaction between CSF Aβ and CSF p-tau levels affecting brain structure.
- The stratified correlation analyses showed that the relationship between p-tau and CTh is modified by Aβ status and the relationship between Aβ and CTh is modified by p-tau status. p-Tau-dependent thinning was found in different cortical regions in Aβ(+) subjects but not in Aβ(-) subjects.
- Interpretation Our data suggest that interactions between biomarkers in AD result in a 2-phase phenomenon of pathological cortical thickening associated with low CSF Aβ, followed by atrophy once CSF p-tau becomes abnormal.
Why it matters
In these normal controls, cortical atrophy occurred only in people with both abnormal CSF β-amyloid and abnormal CSF phospho-tau, and the relationship between each biomarker and cortical thickness depended on the other. This cross-sectional finding suggests these biomarkers interact in preclinical Alzheimer disease, but it cannot show cause or predict outcomes.
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Study details
- Study designcross-sectional
- Participants145
- Evidence strengthLow
How this study scored 56/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 54 of the 96 points we could judge it on, which is 56 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| 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 | 2014 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 145 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 143 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.2 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 3 / 6 | Cited 7.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 12 other studies in this library |
| Still being cited | 2 / 4 | Cited 34 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 1 / 3 | Universitat Autònoma de Barcelona: institution h-index 782 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 24852682) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 54 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 54 of the 96 points we could judge it on is 56 out of 100. |
| Total | 56 / 100 | — |
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