Astrocyte activation imaging with 11C-acetate and amyloid PET in mild cognitive impairment due to Alzheimer pathology.

Michael Tran Duong, Yin Jie Chen, Robert K Doot, Anthony J Young, Hsiaoju Lee, Jenny Cai, Arun Pilania, David A Wolk, Ilya M Nasrallah

Nuclear medicine communications 2021 Nov 01

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Neuroinflammation is a well-known feature of early Alzheimer disease (AD) yet astrocyte activation has not been extensively evaluated with in vivo imaging in mild cognitive impairment (MCI) due to amyloid plaque pathology. Unlike neurons, astrocytes metabolize acetate, which has potential as a glial biomarker in neurodegeneration in response to AD pathologic features. Since the medial temporal lobe (MTL) is a hotspot for AD neurodegeneration and inflammation, we assessed astrocyte activity in the MTL and compared it to amyloid and cognition. We evaluate spatial patterns of in vivo astrocyte activation and their relationships to amyloid deposition and cognition in a cross-sectional pilot study of six participants with MCI and five cognitively normal participants. We measure 11C-acetate and 18F-florbetaben amyloid standardized uptake values ratios (SUVRs) and kinetic flux compared to the cerebellum on PET, with MRI and neurocognitive testing. MTL 11C-acetate SUVR was significantly elevated in MCI compared to cognitively normal participants (P = 0.03; Cohen d = 1.76). Moreover, MTL 11C-acetate SUVR displayed significant associations with global and regional amyloid burden in MCI. Greater MTL 11C-acetate retention was significantly related with worse neurocognitive measures including the Montreal Cognitive Assessment (P = 0.001), word list recall memory (P = 0.03), Boston naming test (P = 0.04) and trails B test (P = 0.04). While further validation is required, this exploratory pilot study suggests a potential role for 11C-acetate PET as a neuroinflammatory biomarker in MCI and early AD to provide clinical and translational insights into astrocyte activation as a pathological response to amyloid. Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Citation

Michael Tran Duong, Yin Jie Chen, Robert K Doot, Anthony J Young, Hsiaoju Lee, Jenny Cai, Arun Pilania, David A Wolk, Ilya M Nasrallah. Astrocyte activation imaging with 11C-acetate and amyloid PET in mild cognitive impairment due to Alzheimer pathology. Nuclear medicine communications. 2021 Nov 01;42(11):1261-1269