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Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults
Albrecht DS, Sagare A, Pachicano M, Sweeney MD, Toga A, Zlokovic B, Chui H, Joe E et al.. Brain, behavior, and immunity, 2021-01-22
Topic: Brain proteins, microglia and lab models
CNS inflammation is a key factor in Alzheimer's Disease (AD), but its relation to pathological Aβ, tau, and APOE4 is poorly understood, particularly prior to the onset of cognitive symptoms. To better characterize early relationships between inflammation, APOE4, and AD pathology, we assessed correlations between cerebrospinal fluid (CSF) inflammatory markers and brain levels of Aβ and tau in cognitively normal older adults. Each participant received a lumbar puncture to collect and quantify CSF levels of TNFα, IL-6, IL-8, and IL-10, a T1-weighted MRI, and PET scanning with [ 18 F]flortaucipir (FTP; n = 57), which binds to tau tangles and/or [ 18 F]florbetapir (FBP; n = 58), which binds to Aβ. Parallel voxelwise regressions assessed relationships between each CSF inflammatory marker and FTP and FBP SUVR, as well as APOE4*CSF inflammation interactions. Unexpectedly, we detected significant negative associations between regional Aβ and tau PET uptake and CSF inflammatory markers. For Aβ PET, we detected negative associations with CSF IL-6 and IL-8 in regions known to show early accumulation of Aβ (i.e. lateral and medial frontal lobes). For tau PET, negative relationships were observed with CSF TNFα and IL-8, predominantly in regions known to exhibit early tau accumulation (i.e. medial temporal lobe). In subsequent analyses, significant interactions between APOE4 status and IL-8 on Aβ and tau PET levels were observed in spatially distinct regions from those showing CSF-Aβ/tau relationships. Results from the current cross-sectional study support previous findings that neuroinflammation may be protective against AD pathology at a given stage of the disease, and extend these findings to a cognitively normal aging population. This study provides new insight into a dynamic relationship between neuroinflammation and AD pathology and may have implications for whom and when neuroinflammatory therapies may be appropriate.
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APA 7th
Albrecht, D. S., Sagare, A., Pachicano, M., Sweeney, M. D., Toga, A., Zlokovic, B., et al. (2021). Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults. Brain, behavior, and immunity. https://doi.org/10.1016/j.bbi.2021.01.010
Vancouver
Albrecht DS, Sagare A, Pachicano M, Sweeney MD, Toga A, Zlokovic B, et al. Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults. Brain, behavior, and immunity. 2021. doi:10.1016/j.bbi.2021.01.010. PMID: 33486003.
BibTeX
@article{albrecht2021-33486003,
author = {Albrecht, D. S. and Sagare, A. and Pachicano, M. and Sweeney, M. D. and Toga, A. and Zlokovic, B. and Chui, H. and Joe, E. and others},
title = {{Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults}},
journal = {Brain, behavior, and immunity},
year = {2021},
doi = {10.1016/j.bbi.2021.01.010},
pmid = {33486003},
url = {https://doi.org/10.1016/j.bbi.2021.01.010}
}
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Key findings
- Unexpectedly, we detected significant negative associations between regional Aβ and tau PET uptake and CSF inflammatory markers.
- In subsequent analyses, significant interactions between APOE4 status and IL-8 on Aβ and tau PET levels were observed in spatially distinct regions from those showing CSF-Aβ/tau relationships.
- Results from the current cross-sectional study support previous findings that neuroinflammation may be protective against AD pathology at a given stage of the disease, and extend these findings to a cognitively normal aging population.
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Study details
- Study designcross-sectional
- Participants57
- Evidence strengthLow
How this study scored 53/100
Published in a peer-reviewed 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 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 31 of the 58 points we could judge it on, which is 53 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Brain, behavior, and immunity) |
| 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 | 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 | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 1 / 4 | 57 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 | — / 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 33486003) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 31 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 31 of the 58 points we could judge it on is 53 out of 100. |
| Total | 53 / 100 | — |
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