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Microglial activation correlates in vivo with both tau and amyloid in Alzheimer's disease
Dani M, Wood M, Mizoguchi R, Fan Z, Walker Z, Morgan R, Hinz R, Biju M et al.. Brain : a journal of neurology, 2018-09-01
Topic: Brain proteins, microglia and lab models
Plain-language summary
Alzheimer's disease is characterized by the histopathological presence of amyloid-β plaques and tau-containing neurofibrillary tangles. Microglial activation is also a recognized pathological component. The relationship between microglial activation and protein aggregation is still debated. We investigated the relationship between amyloid plaques, tau tangles and activated microglia using PET imaging. Fifty-one subjects (19 healthy controls, 16 mild cognitive impairment and 16 Alzheimer's disease subjects) participated in the study. All subjects had neuropsychometric testing, MRI, amyloid (18F-flutemetamol), and microglial (11C-PBR28) PET. All subjects with mild cognitive impairment and Alzheimer's disease and eight of the controls had tau (18F-AV1451) PET. 11C-PBR28 PET was analysed using Logan graphical analysis with an arterial plasma input function, while 18F-flutemetamol and 18F-AV1451 PET were analysed as target:cerebellar ratios to create parametric standardized uptake value ratio maps. Biological parametric mapping in the Statistical Parametric Mapping platform was used to examine correlations between uptake of tracers at a voxel-level. There were significant widespread clusters of positive correlation between levels of microglial activation and tau aggregation in both the mild cognitive impairment (amyloid-positive and amyloid-negative) and Alzheimer's disease subjects. The correlations were stronger in Alzheimer's disease than in mild cognitive impairment, suggesting that these pathologies increase together as disease progresses. Levels of microglial activation and amyloid deposition were also correlated, although in a different spatial distribution; correlations were stronger in mild cognitive impairment than Alzheimer's subjects, in line with a plateauing of amyloid load with disease progression. Clusters of positive correlations between microglial activation and protein aggregation often targeted similar areas of association cortex, indicating that all three processes are present in specific vulnerable brain areas. For the first time using PET imaging, we show that microglial activation can correlate with both tau aggregation and amyloid deposition. This confirms the complex relationship between these processes. These results suggest that preventative treatment for Alzheimer's disease should target all three processes.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Dani, M., Wood, M., Mizoguchi, R., Fan, Z., Walker, Z., Morgan, R., et al. (2018). Microglial activation correlates in vivo with both tau and amyloid in Alzheimer's disease. Brain : a journal of neurology. https://doi.org/10.1093/brain/awy188
Vancouver
Dani M, Wood M, Mizoguchi R, Fan Z, Walker Z, Morgan R, et al. Microglial activation correlates in vivo with both tau and amyloid in Alzheimer's disease. Brain : a journal of neurology. 2018. doi:10.1093/brain/awy188. PMID: 30052812.
BibTeX
@article{dani2018-30052812,
author = {Dani, M. and Wood, M. and Mizoguchi, R. and Fan, Z. and Walker, Z. and Morgan, R. and Hinz, R. and Biju, M. and others},
title = {{Microglial activation correlates in vivo with both tau and amyloid in Alzheimer's disease}},
journal = {Brain : a journal of neurology},
year = {2018},
doi = {10.1093/brain/awy188},
pmid = {30052812},
url = {https://doi.org/10.1093/brain/awy188}
}
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Key findings
- There were significant widespread clusters of positive correlation between levels of microglial activation and tau aggregation in both the mild cognitive impairment (amyloid-positive and amyloid-negative) and Alzheimer's disease subjects.
- The correlations were stronger in Alzheimer's disease than in mild cognitive impairment, suggesting that these pathologies increase together as disease progresses.
- These results suggest that preventative treatment for Alzheimer's disease should target all three processes.
Why it matters
In people with mild cognitive impairment and Alzheimer's disease, brain imaging showed that microglial activation was correlated with both tau and amyloid accumulation. This suggests all three processes increase together, but the study does not show that targeting them prevents or treats the disease.
Study details
- Evidence strengthLow
How this study scored 54/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| 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 | 2018 — 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 | 5 / 7 | Cited 268 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 26.8 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 14.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 17 other studies in this library |
| Still being cited | 3 / 4 | Cited 78 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Paul Edison: h-index 53 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 30052812) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
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