# Assessing neuroinflammation in Alzheimer's disease: A TSPO‐PET study using ER176 and its correlation with amyloid and tau pathology

## TL;DR

This study uses ER176 PET imaging to show that neuroinflammation increases with Alzheimer's disease progression and is linked to amyloid and tau pathology.

## Contribution

The study demonstrates ER176's utility in detecting early and progressive neuroinflammation in Alzheimer's disease.

## Key findings

- Neuroinflammation is higher in cognitively unimpaired individuals with amyloid positivity compared to those without.
- Alzheimer's disease shows more widespread neuroinflammation in temporal, occipital, and parietal lobes.
- Neuroinflammation correlates with both amyloid and tau pathology as the disease progresses.

## Abstract

Neuroinflammation plays a crucial role in neuronal damage, synaptic dysfunction, and impaired neurogenesis, significantly contributing to Alzheimer's Disease (AD) progression. To address this, we assessed ER176's effectiveness in detecting neuroinflammation in cognitively unimpaired (CU) A–, CU A+, mild cognitive impairment (MCI), and AD participants, with a particular focus on their amyloid and tau status. This research aims to help identify suitable candidates for specialized treatment when adversely impacted by neuroinflammation.

Participants from the Mayo Clinic Study of Aging were recruited for this study. The study included four participant groups: CU A– (n = 25), CU A+ (n = 25), MCI A+ (n = 25), and AD (n = 15). We explored the variations in neuroinflammation PET results among different groups.

When compared to CU A–, both CU A+ and MCI A+ groups (Figure 1) showed greater regional neuroinflammation. AD exhibited more widely affected regions with neuroinflammation (temporal, occipital, and parietal lobes) than CU A‐ over the PVC spectrum (Figure 1). Minimally more neuroinflammation was seen (temporal lobes) in MCI A+ than CU A+ (Figure 1). AD had more widespread regional neuroinflammation vs CU A+ (Figure 1) than in MCI A+ vs CU+. The least difference in neuroinflammation is seen in MCI A+ vs AD (Figure 1). For A+ vs A‐, A+ showed more widespread neuroinflammation (Figure 2). T+ (tau>=1.29) vs T‐ (tau<1.29) showed more neuro inflammation with T+ (Figure 2). Comparisons varied modestly in significance level with PVC method (Figures 1 and 2).

The findings demonstrate that neuroinflammatory changes are associated with AD pathology. Even at early stages, neuroinflammation is associated with CU+. As the condition progresses, neuroinflammation extends to more brain regions and is associated with increased A+ and T+ pathology in MCI A+ and AD. These results suggest an early and persistent role of neuroinflammation in the progression AD pathology, indicating that therapy options could include early anti‐inflammatory intervention, even prior to clinical symptoms, along with treatment during clinical manifestations. PVC methods used may provide somewhat variable results.