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Longitudinal influence of microglial activation and amyloid on neuronal function in Alzheimer's disease
Fan Z, Okello AA, Brooks DJ, Edison P.. Brain : a journal of neurology, 2015-10-27
Topic: Amyloid, tau and blood-test diagnosis
Amyloid deposition, tangle formation, neuroinflammation and neuronal dysfunction are pathological processes involved in Alzheimer's disease. However, the relative role of these processes in driving disease progression is still unclear. The aim of this positron emission tomography study was to: (i) investigate longitudinal changes of microglial activation, amyloid and glucose metabolism; and (ii) assess the temporospatial relationship between these three processes in Alzheimer's disease. A group of eight patients with a diagnosis of Alzheimer's disease (66 ± 4.8 years) and 14 healthy controls (65 ± 5.5 years) underwent T1 and T2 magnetic resonance imaging, along with (11)C-(R)-PK11195, (11)C-Pittsburgh compound B and (18)F-fluorodeoxyglucose positron emission tomography scans for microglial activation, amyloid deposition and glucose metabolism. All patients were followed-up with repeated magnetic resonance imaging and three positron emission tomography scans after 16 months. Parametric maps were interrogated using region of interest analysis, Statistical Parametric Mapping, and between-group correlation analysis at voxel-level using Biological Parametric Mapping. At baseline, patients with Alzheimer's disease showed significantly increased microglial activation compared to the control subjects. During follow-up, for the first time, we found that while there is a progressive reduction of glucose metabolism, there was a longitudinal increase of microglial activation in the majority of the patients with Alzheimer's disease. Voxel-wise correlation analysis revealed that microglial activation in patients with Alzheimer's disease was positively correlated with amyloid deposition and inversely correlated with regional cerebral metabolic rate at voxel level over time. Even though one of the limitations of this study is the lack of longitudinal follow-up of healthy control subjects, this study demonstrates that there is persistent neuroinflammation throughout the Alzheimer's disease process with associated synaptic dysfunction and reduced glucose metabolism. Voxel-wise correlation analysis suggests that neuroinflammation is associated with localized amyloid deposition and glucose metabolism over time, however, the level of inflammation could also occur independently of amyloid pathology, especially in the later stages of Alzheimer's disease.
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APA 7th
Fan, Z., Okello, A. A., Brooks, D. J., & Edison, P. (2015). Longitudinal influence of microglial activation and amyloid on neuronal function in Alzheimer's disease. Brain : a journal of neurology. https://doi.org/10.1093/brain/awv288
Vancouver
Fan Z, Okello AA, Brooks DJ, Edison P. Longitudinal influence of microglial activation and amyloid on neuronal function in Alzheimer's disease. Brain : a journal of neurology. 2015. doi:10.1093/brain/awv288. PMID: 26510952.
BibTeX
@article{fan2015-26510952,
author = {Fan, Z. and Okello, A. A. and Brooks, D. J. and Edison, P.},
title = {{Longitudinal influence of microglial activation and amyloid on neuronal function in Alzheimer's disease}},
journal = {Brain : a journal of neurology},
year = {2015},
doi = {10.1093/brain/awv288},
pmid = {26510952},
url = {https://doi.org/10.1093/brain/awv288}
}
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Key findings
- At baseline, patients with Alzheimer's disease showed significantly increased microglial activation compared to the control subjects.
- During follow-up, for the first time, we found that while there is a progressive reduction of glucose metabolism, there was a longitudinal increase of microglial activation in the majority of the patients with Alzheimer's disease.
- Voxel-wise correlation analysis revealed that microglial activation in patients with Alzheimer's disease was positively correlated with amyloid deposition and inversely correlated with regional cerebral metabolic rate at voxel level over time.
- Voxel-wise correlation analysis suggests that neuroinflammation is associated with localized amyloid deposition and glucose metabolism over time, however, the level of inflammation could also occur independently of amyloid pathology, especially in the later stages of Alzheimer's disease.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 55/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people 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 32 of the 58 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| 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 | 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 | — / 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 26510952) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 32 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 32 of the 58 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
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