Association between neurite metrics and tau/inflammatory pathology in Alzheimer's disease

INTRODUCTION: The molecular mechanism of neurodegeneration, including tau and neurite complexity, is an important topic in Alzheimer's disease (AD) research. METHODS: We recruited 27 amyloid‐positive individuals identified through (11)C‐Pittsburgh compound B (PiB) positron emission tomography (PET) and 31 amyloid‐negative individuals with normal cognition. All participants underwent (11)C‐PiB and (18)F‐THK5351 PET and magnetic resonance imaging (MRI) with neurite orientation dispersion and density imaging (NODDI) protocol. The neurite density index (NDI), orientation dispersion index (ODI), and PET images were analyzed to calculate voxel‐wise correlations among the imaging modalities and correlations with cognitions. RESULTS: In the amyloid‐positive participants, there were significant negative correlations between (18)F‐THK5351 and NDI and between (18)F‐THK5351 and ODI. The bilateral mesial and lateral temporal lobes were mainly involved. Regarding cognition, (18)F‐THK5351 showed more marked associations with all cognitive domains than the other modalities. DISCUSSION: Tau and neuroinflammation in AD may reduce the neurite density and orientation dispersion, particularly in the mesial and lateral temporal lobes.