Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer's disease
Open accessAbstract
See Kreisl (doi:10.1093/awx151) for a scientific commentary on this article.Subjects with mild cognitive impairment associated with cortical amyloid-β have a greatly increased risk of progressing to Alzheimer's disease. We hypothesized that neuroinflammation occurs early in Alzheimer's disease and would be present in most amyloid-positive mild cognitive impairment cases. 11C-Pittsburgh compound B and 11C-(R)-PK11195 positron emission tomography was used to determine the amyloid load and detect the extent of neuroinflammation (microglial activation) in 42 mild cognitive impairment cases. Twelve age-matched healthy control subjects had 11C-Pittsburgh compound B and 10 healthy control subjects had 11C-(R)-PK11195 positron emission tomography for comparison. Amyloid-positivity was defined as 11C-Pittsburgh compound B target-to-cerebellar ratio above 1.5 within a composite cortical volume of interest. Supervised cluster analysis was used to generate parametric maps of 11C-(R)-PK11195 binding potential. Levels of 11C-(R)-PK11195 binding potential were measured in a selection of cortical volumes of interest and at a voxel level. Twenty-six (62%) of 42 mild cognitive impairment cases showed a raised cortical amyloid load compared to healthy controls. Twenty-two (85%) of the 26 amyloid-positive mild cognitive impairment cases showed clusters of increased cortical microglial activation accompanying the amyloid. There was a positive correlation between levels of amyloid load and 11C-(R)-PK11195 binding potentials at a voxel level within subregions of frontal, parietal and temporal cortices. 11C-(R)-PK11195 positron emission tomography reveals increased inflammation in a majority of amyloid positive mild cognitive impairment cases, its cortical distribution overlapping that of amyloid deposition.
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Higher HDL cholesterol might protect against vascular risk and inflammation accompanying amyloid-β pathology in mild cognitive impairment.
“Higher HDL cholesterol might protect against vascular risk and inflammation accompanying amyloid-β (Aβ) pathology in mild cognitive impairment.26”
From Dementia prevention, intervention, and care: 2020 report of the Lancet Commission (2020) · cites this paper as [26]
The Discussion reports that neuroinflammation accompanies amyloid-β in a majority of amyloid-positive mild cognitive impairment cases. It does not support the claim that higher HDL cholesterol protects against that inflammation or vascular risk; searches for HDL, cholesterol, and vascular risk found no such finding in our copy. The supplied Discussion passage has no page number. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn MCI, microglial activation is positively correlated with amyloid load.
“In MCI, microglial activation was positively correlated with amyloid load.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [141]
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- Authors
- Parbo, P., Ismail, R., Hansen, K. V., Amidi, A., Mårup, F. H., Gottrup, H., Brændgaard, H., Eriksson, B. O., Eskildsen, S. F., Lund, T. E., Tietze, A., Edison, P., Pavese, N., Stokholm, M. G., Borghammer, P., Hinz, R., Aanerud, J., & Brooks, D. J.
- Affiliations
- Aarhus University Hospital (DK)
- Aarhus University (DK)
- Regional Hospital Central Jutland (DK)
- Charité – Universitätsmedizin Berlin (DE)
- Imperial College London (GB)
- University of Manchester (GB)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-05-28
- Volume
- 140
- Issue
- 7
- Pages
- 2002-2011
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2617650278
- Cited by
- 199
- References
- 31
- Citations by year
- 2026: 17 · 2025: 13 · 2024: 23 · 2023: 19 · 2022: 22 · 2021: 29 · 2020: 28 · 2019: 19 · 2018: 26 · 2017: 3
- FWCI
- 17.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Scopus (Elsevier) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by-nc)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- mild cognitive impairment, Alzheimer's disease, neuroinflammation, microglial activation, 11C-Pittsburgh compound B, [11C](R)-PK11195, amyloid load
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Aniline Compounds, Cerebral Cortex, Encephalitis, Female, Humans, Isoquinolines, Male, Middle Aged, Neuropsychological Tests, Thiazoles, Case-Control Studies, Microglia, Disease Progression, Positron-Emission Tomography, Cognitive Dysfunction
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