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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright © 2026 Kjeldsen, Madsen, Parbo, Ismail, Aanerud, Kaasing, Damholdt, Eskildsen, Østergaard and Brooks.Background: Alzheimer’s disease (AD) is a continuum between normal health and dementia with a long preclinical phase, during which AD pathologies start to emerge, but where there are not yet any overt symptoms. The hallmark pathologies of AD are extracellular β-amyloid (Aβ) plaques and intra-neuronal neurofibrillary tangles (NFTs). Aβ deposition is present at the preclinical stage. Additionally, raised microglial activation is a key factor in AD. However, its exact timing and role is still unclear. This exploratory study investigated the prevalence of microglial activation and its association with Aβ deposition and memory impairment in preclinical AD. Methods: A total of 19 preclinical AD subjects with no cognitive complaints but abnormal Aβ deposition present on 11C-Pittsburgh Compound B (11C-PiB PET) and 10 healthy subjects with no cognitive complains or abnormal Aβ deposition on 11C-PiB PET underwent 11C-PK11195 PET (11C-PK). Additionally, the preclinical AD subjects underwent formal cognitive testing with sensitive memory tests, including the Rey Auditory Verbal Learning Test, the Rey Complex Figure Test, and the Face-Name Associative Memory Exam. Results: Microglial activation was raised in occipital and parietal cortices in preclinical AD subjects compared to healthy controls (p < 0.01). In the preclinical subjects there were significant positive correlations between Aβ load and microglial activation in parietal areas (p < 0.01). Finally, in the preclinical subjects, there were significant negative correlations between microglial activation and memory test performance in selected cortical areas (p < 0.01). Conclusion: Microglial activation was significantly raised in preclinical AD cases with no cognitive complaints and associated with impaired memory test performance. This suggests that microglial activation is present before overt clinical symptoms emerge and may be detrimental to cognition even at this early stage.
Author(s): Kjeldsen PL, Madsen LS, Parbo P, Ismail R, Aanerud JFA, Kaasing M, Damholdt MF, Eskildsen SF, Ostergaard L, Brooks DJ
Publication type: Article
Publication status: Published
Journal: Frontiers in Dementia
Year: 2026
Volume: 4
Online publication date: 27/01/2026
Acceptance date: 29/12/2025
Date deposited: 24/02/2026
ISSN (electronic): 2813-3919
Publisher: Frontiers Media SA
URL: https://doi.org/10.3389/frdem.2025.1745571
DOI: 10.3389/frdem.2025.1745571
Data Access Statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
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