Dual association patterns between microglial activation and neuronal health in Alzheimer’s disease: a whole-brain MRSI/PET study

Alzheimers Dement. 2026 Mar;22(3):e71229. doi: 10.1002/alz.71229.

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 (Aβ) 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), [¹ ⁸F]DPA-714, and [¹ ⁸F]AV-45 positron emission tomography (PET). Regional and voxel-wise analyses assessed changes and associations of microglial activation with N-acetylaspartate (NAA) and Aβ.

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 Aβ 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 [¹ ⁸F]DPA-714 PET and NAA, shedding light on the complex interplay between neuroinflammation and neuronal health in AD.

PMID:41795661 | DOI:10.1002/alz.71229

Document this CPD