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Cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF biomarker profile
Milà-Alomà M, Shekari M, Salvadó G, Gispert JD, Arenaza-Urquijo EM, Operto G, Falcon C, Vilor-Tejedor N et al.. Alzheimer's research & therapy, 2021-07-27
Topic: Amyloid, tau and blood-test diagnosis
Background Understanding the changes that occur in the transitional stage between absent and overt amyloid-β (Aβ) pathology within the Alzheimer's continuum is crucial to develop therapeutic and preventive strategies. The objective of this study is to test whether cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF, structural, and functional neuroimaging biomarker profile. Methods Cross-sectional study of 318 middle-aged, cognitively unimpaired individuals from the ALFA+ cohort. We measured CSF Aβ42/40, phosphorylated tau (p-tau), total tau (t-tau), neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, IL6, S100B, and α-synuclein. Participants also underwent cognitive assessments, APOE genotyping, structural MRI, [ 18 F]-FDG, and [ 18 F]-flutemetamol PET. To ensure the robustness of our results, we used three definitions of low burden of Aβ pathology: (1) positive CSF Aβ42/40 and < 30 Centiloids in Aβ PET, (2) positive CSF Aβ42/40 and negative Aβ PET visual read, and (3) 20-40 Centiloid range in Aβ PET. We tested CSF and neuroimaging biomarker differences between the low burden group and the corresponding Aβ-negative group, adjusted by age and sex. Results The prevalence and demographic characteristics of the low burden group differed between the three definitions. CSF p-tau and t-tau were increased in the low burden group compared to the Aβ-negative in all definitions. CSF neurogranin was increased in the low burden group definitions 1 and 3, while CSF NfL was only increased in the low burden group definition 1. None of the defined low burden groups showed signs of atrophy or glucose hypometabolism. Instead, we found slight increases in cortical thickness and metabolism in definition 2. Conclusions There are biologically meaningful Aβ-downstream effects in individuals with a low burden of Aβ pathology, while structural and functional changes are still subtle or absent. These findings support considering individuals with a low burden of Aβ pathology for clinical trials. Trial registration NCT02485730.
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APA 7th
Milà-Alomà, M., Shekari, M., Salvadó, G., Gispert, J. D., Arenaza-Urquijo, E. M., Operto, G., et al. (2021). Cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF biomarker profile. Alzheimer's research & therapy. https://doi.org/10.1186/s13195-021-00863-y
Vancouver
Milà-Alomà M, Shekari M, Salvadó G, Gispert JD, Arenaza-Urquijo EM, Operto G, et al. Cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF biomarker profile. Alzheimer's research & therapy. 2021. doi:10.1186/s13195-021-00863-y. PMID: 34315519.
BibTeX
@article{milaaloma2021-34315519,
author = {Milà-Alomà, M. and Shekari, M. and Salvadó, G. and Gispert, J. D. and Arenaza-Urquijo, E. M. and Operto, G. and Falcon, C. and Vilor-Tejedor, N. and others},
title = {{Cognitively unimpaired individuals with a low burden of Aβ pathology have a distinct CSF biomarker profile}},
journal = {Alzheimer's research \& therapy},
year = {2021},
doi = {10.1186/s13195-021-00863-y},
pmid = {34315519},
url = {https://doi.org/10.1186/s13195-021-00863-y}
}
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Key findings
- To ensure the robustness of our results, we used three definitions of low burden of Aβ pathology: (1) positive CSF Aβ42/40 and < 30 Centiloids in Aβ PET, (2) positive CSF Aβ42/40 and negative Aβ PET visual read, and (3) 20-40 Centiloid range in Aβ PET.
- Results The prevalence and demographic characteristics of the low burden group differed between the three definitions.
- CSF p-tau and t-tau were increased in the low burden group compared to the Aβ-negative in all definitions.
- Instead, we found slight increases in cortical thickness and metabolism in definition 2.
- These findings support considering individuals with a low burden of Aβ pathology for clinical trials.
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Study details
- Study designcross-sectional
- Evidence strengthModerate
How this study scored 59/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for sample size, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 34 of the 58 points we could judge it on, which is 59 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's research & therapy) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 3 / 5 | 2021 — within 6 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 | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34315519) |
| Free to read | 2 / 2 | Free to read |
| Points | 34 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 34 of the 58 points we could judge it on is 59 out of 100. |
| Total | 59 / 100 | — |
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