Abstract
Introduction
Current literature presents conflicting results regarding the impact of neuroinflammation on Alzheimer's disease (AD)-related neurodegeneration. While some studies suggest that neuroinflammation potentiates neurodegeneration, others indicate a protective effect.Methods
We evaluated 145 individuals with positron emission tomography (PET) for amyloid beta (Aβ), tau, and translocator protein (TSPO), a proxy of neuroinflammation, to test the hypothesis that Aβ and tau are associated with the dual effect of neuroinflammation on neurodegeneration across the AD continuum.Results
The detrimental effects of neuroinflammation on gray matter density occurred in two waves. The first neuroinflammation-related detrimental wave was associated with brain Aβ deposition, while the second was with widespread tau tangle pathology. Furthermore, the concomitant presence of neuroinflammation, Aβ, and tau was associated with faster cognitive decline over 2 years.Conclusions
Our results support a model in which Aβ- and tau-associated neuroinflammation are related to two waves of deleterious effects on AD-related neurodegeneration.Highlights
Two waves of detrimental neuroinflammation effects on brain density associated with Aβ or tau. Aβ associated with deleterious effect of neuroinflammation on brain density in early AD. Tau associated with deleterious effect of neuroinflammation on brain density in late AD. Interactions of Aβ, tau, and neuroinflammation are associated with cognitive decline.Citations & impact
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Funding
Funders who supported this work.
Alzheimer's Association (7)
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Grant ID: AARF‐D‐231150249
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Grant ID: 24AACSF‐1200375
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Alzheimer's Society (1)
Grant ID: GBHI ALZ UK‐23‐971089
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Alzheimer's Association (7)
Grant ID: AARF-D-231150249
publications
Grant ID: AARFD-22-974627
publications
Grant ID: 24AACSF-1200375
publications
Grant ID: AARFD-22-923814
publications
Grant ID: 24AARFD-1243899
publications
Grant ID: AARFD-24-1307995
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Grant ID: AARGD-21-850670
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Alzheimer's Society (1)
Grant ID: GBHI ALZ UK-23-971089
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CIHR-CCNA Canadian Consortium of Neurodegeneration in Aging (1)
Grant ID: 200691/2021-0
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Fonds de Recherche du Québec - Santé (1)
Grant ID: 2020-VICO-279314
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Fundação de Amparo a pesquisa do Rio Grande do Sul (1)
Grant ID: 21/2551-0000673-0
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Global Brain Health Institute
Instituto Serrapilheira (2)
Grant ID: Serra-1912-31365
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Grant ID: Serra‐1912‐31365
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NIA NIH HHS (3)
Grant ID: R01AG075336
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Grant ID: R01AG073267
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Grant ID: AG025204-17
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National Academy of Neuropsychology (2)
Grant ID: ALZ-NAN-22-928381
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Grant ID: ALZ‐NAN‐22‐928381
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National Institute on Aging (3)
Grant ID: R01AG073267
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Grant ID: AG025204‐17
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Grant ID: R01AG075336
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