Amyloid beta and tau are associated with the dual effect of neuroinflammation on neurodegeneration
Jan 1, 2025·,,,,,,,,,,
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Guilherme Povala
Bruna Bellaver
Marco Antônio De Bastiani
João Pedro Ferrari-Souza
Cristiano Schaffer Aguzzoli
Douglas Teixeira Leffa
Pamela C. L. Ferreira
Firoza Z. Lussier
Andreia Rocha
Hussein Zalzale
Carolina Soares
Guilherme Bauer-Negrini
Joseph Therriault
Nesrine Rahmouni
Jenna Stevenson
Stijn Servaes
Cécile Tissot
Bruno Zatt
Thomas K. Karikari
Milos D. Ikonomovic
Victor L. Villemagne
Serge Gauthier
Eduardo R. Zimmer
Dana L. Tudorascu
Andréa L. Benedet
Pedro Rosa-Neto
Tharick A. Pascoal
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.
Type
Publication
Alzheimer’s & Dementia
Status
Peer-reviewed
Authors
Biomedical Data Scientist
Computational neuroscientist working at the intersection of machine learning, biomedical
imaging, and human genetics in neurodegenerative disease. My work applies deep learning to
high-dimensional medical images, harmonizes imaging measurements across sites and acquisition
protocols, and integrates imaging with genomic, proteomic, and longitudinal clinical data to
characterise Alzheimer’s disease and related dementias, with particular focus on fluid and
imaging biomarkers of neurodegeneration.