Evidence for Astrocytosis in Prodromal Alzheimer Disease Provided by ¹¹C-Deuterium-L-Deprenyl: A Multitracer PET Paradigm Combining ¹¹C-Pittsburgh Compound B and ¹⁸F-FDG

Abstract

Astrocytes colocalize with fibrillar amyloid-β (Aβ) plaques in postmortem Alzheimer disease (AD) brain tissue. It is therefore of great interest to develop a PET tracer for visualizing astrocytes in vivo, enabling the study of the regional distribution of both astrocytes and fibrillar Aβ. A multitracer PET investigation was conducted for patients with mild cognitive impairment (MCI), patients with mild AD, and healthy controls using ¹¹C-deuterium-L-deprenyl (¹¹C-DED) to measure monoamine oxidase B located in astrocytes. Along with ¹¹C-DED PET, ¹¹C-Pittsburgh compound B (¹¹C-PIB; fibrillar Aβ deposition), ¹⁸F-FDG (glucose metabolism), T1 MRI, cerebrospinal fluid, and neuropsychologic data were acquired from the patients. Methods: ¹¹C-DED PET was performed in MCI patients (n = 8; mean age ± SD, 62.6 ± 7.5 y; mean Mini Mental State Examination, 27.5 ± 2.1), AD patients (n = 7; mean age, 65.1 ± 6.3 y; mean Mini Mental State Examination, 24.4 ± 5.7), and healthy age-matched controls (n = 14; mean age, 64.7 ± 3.6 y). A modified reference Patlak model, with cerebellar gray matter as a reference, was chosen for kinetic analysis of the ¹¹C-DED data. ¹¹C-DED data from 20 to 60 min were analyzed using a digital brain atlas. Mean regional ¹⁸F-FDG uptake and ¹¹C-PIB retention were calculated for each patient, with cerebellar gray matter as a reference. Results: ANOVA analysis of the regional ¹¹C-DED binding data revealed a significant group effect in the bilateral frontal and bilateral parietal cortices related to increased binding in the MCI patients. All patients, except 3 with MCI, showed high ¹¹C-PIB retention. Increased ¹¹C-DED binding in most cortical and subcortical regions was observed in MCI ¹¹C-PIB+ patients relative to controls, MCI ¹¹C-PIB (negative) patients, and AD patients. No regional correlations were found between the 3 PET tracers. Conclusion: Increased ¹¹C-DED binding throughout the brain of the MCI ¹¹C-PIB+ patients potentially suggests that astrocytosis is an early phenomenon in AD development.