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Fluid biomarker-based molecular phenotyping of Alzheimer's disease patients in research and clinical settings
Blennow K, Zetterberg H.. Progress in molecular biology and translational science, 2019-07-24
Topic: Amyloid, tau and blood-test diagnosis
Alzheimer's disease (AD) is very difficult to diagnose on pure clinical grounds, especially in the earlier phases of the disease. At the same time, lessons from recent clinical trials suggest that treatments have to be initiated very early, to have a chance to show clinical efficacy. Therefore, biomarkers reflecting core AD pathophysiology have a key position in clinical trials and clinical management. The core AD cerebrospinal fluid (CSF) biomarker toolbox include amyloid β (Aβ42 and the Aβ42/40 ratio) reflecting brain amyloidosis, total tau (T-tau) reflecting neurodegeneration intensity, and phosphorylated tau (P-tau) that is related to tau pathology. These CSF biomarkers have very consistently been found to have high diagnostic accuracy, also in earlier disease stages. Importantly, CSF Aβ42 and Aβ42/40 ratio show excellent agreement with amyloid PET readouts, indicating that these biomarker tests can be used interchangeably. Intense collaborative standardization efforts have given Certified Reference Materials (CRMs) to harmonize assay formats for CSF Aβ42, the most central AD biomarker, and CRMs for Aβ40 are under development. The core AD biomarkers are today available on high-precision fully automated analytical platforms, which will serve to introduce uniform cut-off levels and enable the large-scale introduction of CSF biomarkers for routine disease diagnosis. Of novel biomarker candidates, synaptic proteins, such as the dendritic protein neurogranin, show promise as tools to monitor synaptic degeneration, an important aspect of AD pathophysiology. Recent studies show that the core AD biomarkers also can be measured in blood samples. Ultra-sensitive assays that allow for quantification of neuronal proteins, such as tau and neurofilament light (NFL) in blood samples. Further, plasma Aβ42 and Aβ42/40 show high concordance with brain amyloidosis evaluated by PET scans. In the future, blood biomarkers may have value as screening tools, especially to rule out patients without biomarker evidence of AD pathology.
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APA 7th
Blennow, K., & Zetterberg, H. (2019). Fluid biomarker-based molecular phenotyping of Alzheimer's disease patients in research and clinical settings. Progress in molecular biology and translational science. https://doi.org/10.1016/bs.pmbts.2019.07.006
Vancouver
Blennow K, Zetterberg H. Fluid biomarker-based molecular phenotyping of Alzheimer's disease patients in research and clinical settings. Progress in molecular biology and translational science. 2019. doi:10.1016/bs.pmbts.2019.07.006. PMID: 31699324.
BibTeX
@article{blennow2019-31699324,
author = {Blennow, K. and Zetterberg, H.},
title = {{Fluid biomarker-based molecular phenotyping of Alzheimer's disease patients in research and clinical settings}},
journal = {Progress in molecular biology and translational science},
year = {2019},
doi = {10.1016/bs.pmbts.2019.07.006},
pmid = {31699324},
url = {https://doi.org/10.1016/bs.pmbts.2019.07.006}
}
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Key findings
- At the same time, lessons from recent clinical trials suggest that treatments have to be initiated very early, to have a chance to show clinical efficacy.
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Study details
- Evidence strengthLow
How this study scored 38/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / 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 multicenter collaboration, so those were left out: it earned 22 of the 58 points we could judge it on, which is 38 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Progress in molecular biology and translational science) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 2 / 5 | 2019 — within 10 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) |
| Randomized / blinded | 0 / 2 | No randomization 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31699324) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 22 of the 58 points we could judge it on is 38 out of 100. |
| Total | 38 / 100 | — |
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