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Decreased CSF clearance and increased brain amyloid in Alzheimer's disease
Li Y, Rusinek H, Butler T, Glodzik L, Pirraglia E, Babich J, Mozley PD, Nehmeh S et al.. Fluids and barriers of the CNS, 2022-03-14
Topic: Amyloid, tau and blood-test diagnosis
Background In sporadic Alzheimer's disease (AD), brain amyloid-beta (Aβ) deposition is believed to be a consequence of impaired Aβ clearance, but this relationship is not well established in living humans. CSF clearance, a major feature of brain glymphatic clearance (BGC), has been shown to be abnormal in AD murine models. MRI phase contrast and intrathecally delivered contrast studies have reported reduced CSF flow in AD. Using PET and tau tracer 18 F-THK5117, we previously reported that the ventricular CSF clearance of the PET tracer was reduced in AD and associated with elevated brain Aβ levels. Methods In the present study, we use two PET tracers, 18 F-THK5351 and 11 C-PiB to estimate CSF clearance calculated from early dynamic PET frames in 9 normal controls and 15 AD participants. Results we observed that the ventricular CSF clearance measures were correlated (r = 0.66, p < 0.01), with reductions in AD of 18 and 27%, respectively. We also replicated a significant relationship between ventricular CSF clearance ( 18 F-THK5351) and brain Aβ load (r = - 0.64, n = 24, p < 0.01). With a larger sample size, we extended our observations to show that reduced CSF clearance is associated with reductions in cortical thickness and cognitive performance. Conclusions Overall, the findings support the hypothesis that failed CSF clearance is a feature of AD that is related to Aβ deposition and to the pathology of AD. Longitudinal studies are needed to determine whether failed CSF clearance is a predictor of progressive amyloidosis or its consequence.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Li, Y., Rusinek, H., Butler, T., Glodzik, L., Pirraglia, E., Babich, J., et al. (2022). Decreased CSF clearance and increased brain amyloid in Alzheimer's disease. Fluids and barriers of the CNS. https://doi.org/10.1186/s12987-022-00318-y
Vancouver
Li Y, Rusinek H, Butler T, Glodzik L, Pirraglia E, Babich J, et al. Decreased CSF clearance and increased brain amyloid in Alzheimer's disease. Fluids and barriers of the CNS. 2022. doi:10.1186/s12987-022-00318-y. PMID: 35287702.
BibTeX
@article{li2022-35287702,
author = {Li, Y. and Rusinek, H. and Butler, T. and Glodzik, L. and Pirraglia, E. and Babich, J. and Mozley, P. D. and Nehmeh, S. and others},
title = {{Decreased CSF clearance and increased brain amyloid in Alzheimer's disease}},
journal = {Fluids and barriers of the CNS},
year = {2022},
doi = {10.1186/s12987-022-00318-y},
pmid = {35287702},
url = {https://doi.org/10.1186/s12987-022-00318-y}
}
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Key findings
- Using PET and tau tracer 18 F-THK5117, we previously reported that the ventricular CSF clearance of the PET tracer was reduced in AD and associated with elevated brain Aβ levels.
- Results we observed that the ventricular CSF clearance measures were correlated (r = 0.66, p < 0.01), with reductions in AD of 18 and 27%, respectively.
- We also replicated a significant relationship between ventricular CSF clearance ( 18 F-THK5351) and brain Aβ load (r = - 0.64, n = 24, p < 0.01).
- With a larger sample size, we extended our observations to show that reduced CSF clearance is associated with reductions in cortical thickness and cognitive performance.
- Conclusions Overall, the findings support the hypothesis that failed CSF clearance is a feature of AD that is related to Aβ deposition and to the pathology of AD.
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Study details
- Study designlongitudinal study
- Participants24
- Evidence strengthModerate
How this study scored 66/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported 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 38 of the 58 points we could judge it on, which is 66 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Fluids and barriers of the CNS) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 7 / 12 | A longitudinal study following the same people over 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 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 24 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) |
| 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 35287702) |
| Free to read | 2 / 2 | Free to read |
| Points | 38 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 38 of the 58 points we could judge it on is 66 out of 100. |
| Total | 66 / 100 | — |
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