Neuroinflammation demonstrated by 11C-ER176 PET with amyloid and tau pathology.

INTRODUCTION

Understanding neuroinflammation across the Alzheimer's disease (AD) spectrum is essential to elucidate disease mechanisms and individualize therapy.

METHODS

Human microglial translocator protein (TSPO) expression under inflammatory stimuli was assessed by immunoblot experiments. Ninety-six participants were enrolled across four groups: cognitively unimpaired amyloid (CU A) + and -, mild cognitive impaired (MCI) A+, and Alzheimer's disease dementia (ADD) A+. Neuroinflammation using 11C-ER176 TSPO positron emission tomography (PET) was compared to amyloid and tau PET. Correlations between neuroinflammation, amyloid, and tau pathology were examined across disease stages.

RESULTS

TSPO was upregulated in human microglia under AD-like inflammatory conditions. Neuroinflammation, defined by PET TSPO, increased in CU A+ participants and became more widespread with increasing disease severity, aligning with worsening amyloid and tau pathology. Associations with tau were particularly extensive in temporal and parietal regions.

DISCUSSION: These findings suggest probable amyloid association with early microglial activation, while tau pathology is closely tied to wider distribution of neuroinflammation.

HIGHLIGHTS: TSPO expression increases in human microglia under AD-like inflammation. 11C-ER176 PET shows stage-dependent neuroinflammation across the AD spectrum. Neuroinflammation overlaps with tau and is more widespread in amyloid-positive individuals. Activity peaks in MCI, stabilizes later, and relates to vascular and neurodegenerative changes.