Does inflammation precede tau aggregation in early Alzheimer's disease? A PET study
Open accessAbstract
Objective Our aim was to assess with positron emission tomography (PET) the temporal and spatial inter-relationships between levels of cortical microglial activation and the aggregated amyloid-β and tau load in mild cognitive impairment (MCI) and early Alzheimer's disease (AD).Methods Six clinically probable AD and 20 MCI subjects had inflammation (11 C-(R)-PK11195), amyloid (11 C-PiB) and tau (18 F-flortaucipir) PET, magnetic resonance imaging (MRI) and a neuropsychological assessment. Parametric images of tracer binding were interrogated at a voxel level and by region of interest analyses.Results 55% of MCI and 83% of AD subjects had a high amyloid-β load. We have previously reported that clusters of correlated amyloid and inflammation levels are present in cortex. Here we found no correlation between levels of inflammation (11 C-(R)-PK11195 BP ND) and tau (18 F-flortaucipir SUVR) or MMSE scores in high amyloid-β cases.Interpretation While correlated levels of amyloid-β and inflammation can be seen in MCI, we did not detect an association between levels of cortical tau tangles and inflammation in our series of high amyloid-β cases. High levels of inflammation could be seen in amyloid-β positive MCI cases where 18 F-flortaucipir signals were low suggesting microglial activation precedes tau tangle formation. Inflammation levels were higher in high amyloid-β MCI than in early AD cases, compatible with it initially playing a protective role.
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- Authors
- Parbo, P., Ismail, R., Sommerauer, M., Stokholm, M. G., Hansen, A. K., Hansen, K. V., Amidi, A., Schaldemose, J. L., Gottrup, H., Brændgaard, H., Eskildsen, S. F., Borghammer, P., Hinz, R., Aanerud, J., & Brooks, D. J.
- Affiliations
- Aarhus University Hospital (DK)
- Aarhus University (DK)
- University of Manchester (GB)
- Corresponding author
- Parbo, Peter
- ORCID
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 117
- Pages
- 211-216
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2808375651
- Cited by
- 63
- References
- 36
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 5 · 2023: 9 · 2022: 7 · 2021: 7 · 2020: 15 · 2019: 8 · 2018: 1
- FWCI
- 5.49
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Newcastle University ePrints (Newcastle Univesity) (cc-by-nc-nd)
- Funders
- Danish Council of Independent Research (DFF-1331-00184)
- Lundbeck Foundation (R140-2013-13245)
- Aarhus University Research Foundation (AU-16725)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, mild cognitive impairment, neuroinflammation, microglial activation, tau aggregation, amyloid-beta, [11C](R)-PK11195, 18F-flortaucipir, [11C]PIB, cortical inflammation, neuroprotection
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Cross-Sectional Studies, Female, Humans, Inflammation, Male, Middle Aged, tau Proteins, Early Diagnosis, Positron-Emission Tomography, Cognitive Dysfunction, Protein Aggregation, Pathological
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