Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease
Alcolea D, Martínez-Lage P, Sánchez-Juan P, Olazarán J, Antúnez C, Izagirre A, Ecay-Torres M, Estanga A et al.. Neurology, 2015-07-15
Topic: Amyloid, tau and blood-test diagnosis
Objective To investigate CSF markers involved in amyloid precursor protein processing, neuronal damage, and neuroinflammation in the preclinical stages of Alzheimer disease (AD) and participants with suspected non-Alzheimer pathology (SNAP). Methods We collected CSF from 266 cognitively normal volunteers participating in a cross-sectional multicenter study (the SIGNAL study) to investigate markers involved in amyloid precursor protein processing (Aβ42, sAPPβ, β-secretase activity), neuronal damage (total-tau [t-tau], phospho-tau [p-tau]), and neuroinflammation (YKL-40). We analyzed the relationship among biomarkers, clinical variables, and the APOE genotype, and compared biomarker levels across the preclinical stages of the National Institute on Aging-Alzheimer's Association classification: stage 0, 1, 2, 3, and SNAP. Results The median age in the whole cohort was 58.8 years (range 39.8-81.6). Participants in stages 2-3 and SNAP had higher levels of YKL-40 than those in stages 0 and 1. Participants with SNAP had higher levels of sAPPβ than participants in stage 0 and 1. No differences were found between stages 0, 1, and 2-3 in sAPPβ and β-secretase activity in CSF. Age correlated with t-tau, p-tau, and YKL-40. It also correlated with Aβ42, but only in APOE ε4 carriers. Aβ42 correlated positively with t-tau, sAPPβ, and YKL-40 in participants with normal Aβ42. Conclusions Our findings suggest that inflammation in the CNS increases in normal aging and is intimately related to markers of neurodegeneration in the preclinical stages of AD and SNAP. sAPPβ and β-secretase activity are not useful diagnostic or staging markers in preclinical AD.
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APA 7th
Alcolea, D., Martínez-Lage, P., Sánchez-Juan, P., Olazarán, J., Antúnez, C., Izagirre, A., et al. (2015). Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0000000000001859
Vancouver
Alcolea D, Martínez-Lage P, Sánchez-Juan P, Olazarán J, Antúnez C, Izagirre A, et al. Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease. Neurology. 2015. doi:10.1212/wnl.0000000000001859. PMID: 26180139.
BibTeX
@article{alcolea2015-26180139,
author = {Alcolea, D. and Martínez-Lage, P. and Sánchez-Juan, P. and Olazarán, J. and Antúnez, C. and Izagirre, A. and Ecay-Torres, M. and Estanga, A. and others},
title = {{Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease}},
journal = {Neurology},
year = {2015},
doi = {10.1212/wnl.0000000000001859},
pmid = {26180139},
url = {https://doi.org/10.1212/wnl.0000000000001859}
}
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Key findings
- Results The median age in the whole cohort was 58.8 years (range 39.8-81.6).
- Conclusions Our findings suggest that inflammation in the CNS increases in normal aging and is intimately related to markers of neurodegeneration in the preclinical stages of AD and SNAP. sAPPβ and β-secretase activity are not useful diagnostic or staging markers in preclinical AD.
Why it matters
In a single-visit study of spinal fluid from 266 cognitively normal volunteers (median age 58.8), the inflammation marker YKL-40 was higher in people at later preclinical Alzheimer's stages (2-3) and in those with suspected non-Alzheimer pathology than in stages 0 and 1. It also rose with age, so the authors conclude that brain inflammation increases with normal aging and tracks markers of nerve damage early on. Two amyloid-processing measures, sAPPβ and β-secretase activity, did not separate the stages and were judged not useful for staging. These are group associations from one time point, not a diagnostic test or a treatment finding.
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Study details
- Study designcross-sectional
- Evidence strengthModerate
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 sample size, effect reported, studied in people 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 | 4 / 12 | A snapshot of people at one point in time |
| 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 | 2015 — 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 | 5 / 7 | Cited 163 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 12.5 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 13.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 23 other studies in this library |
| Still being cited | 2 / 4 | Cited 27 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Alberto Lleó: h-index 92 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Universitat Autònoma de Barcelona: institution h-index 782 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 26180139) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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