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.
Povala et al. (Mon,) studied this question.