Abstract

INTRODUCTION Microglial activation can either support neuronal function or exacerbate damage, contributing to Alzheimer's disease (AD) progression. We investigated spatial relationships among microglial activation, neuronal health, and amyloid beta (A beta) in the AD spectrum.

METHODS Forty healthy controls, 37 patients with mild cognitive impairment (MCI), and 62 patients with AD underwent whole-brain high-resolution 1H-magnetic resonance spectroscopic imaging (MRSI), [F-18]DPA-714, and [F-18]AV-45 positron emission tomography (PET). Regional and voxel-wise analyses assessed changes and associations of microglial activation with N-acetylaspartate (NAA) and A beta.

RESULTS MCI and AD patients showed higher microglial activation and lower NAA, correlating with cognitive decline. In controls and MCI, microglial activation correlated positively with NAA and A beta in early amyloid-accumulating regions. Conversely, negative correlations with NAA emerged in the hippocampus in MCI and extended to temporal and occipital regions in AD.

DISCUSSION For the first time, we identified two distinct spatial association patterns between [F-18]DPA-714 PET and NAA, shedding light on the complex interplay between neuroinflammation and neuronal health in AD.

FIGURE 1.  Mean maps of whole-brain AV-45 SUVR, DPA-714 SUVR, and NAA across CN, MCI, and AD groups. AD, Alzheimer’s disease; CN,cognitively normal; MCI, mild cognitive impairment; NAA, N-acetylaspartate; SUVR, standardized uptake value ratio.

FIGURE 2. Voxel-wise correlations of microglial activation with neuronal health. Between DPA-714 SUVR and NAA, positive voxel-wise correlations were found in CN, both positive and negative correlations were found in MCI, and only negative correlations were found in AD. Voxel-wise z-score maps were computed for each imaging modality using the reference group as a normative baseline and were subsequently used for intermodal biological parametric mapping analyses. Representative clusters are picked from the superior frontal cortex of the CN group, the superior occipital and hippocampus of the MCI group, and the middle temporal cortex of the AD group. AD, Alzheimer’s disease; CN, cognitively normal; MCI, mild cognitive impairment; NAA, N-acetylaspartate; SUVR, standardized uptake value ratio.

https://doi.org/10.1002/alz.71229