Distinct patterns of increased translocator protein in posterior cortical atrophy and amnestic Alzheimer's disease

Abstract

We sought to determine whether patients with posterior cortical atrophy (PCA) demonstrate a pattern of binding to translocator protein 18 kDa, a marker of microglial activation, that is distinct from that in patients with amnestic presentation of Alzheimer's disease (AD). Eleven PCA patients, 11 amnestic AD patients, and 15 age-matched controls underwent positron emission tomography with 11C-PBR28 to measure translocator protein 18 kDa. PCA patients showed greater 11C-PBR28 binding than controls in occipital, posterior parietal, and temporal regions. In contrast, amnestic AD patients showed greater 11C-PBR28 binding in inferior and medial temporal cortex. Increased 11C-PBR28 binding overlapped with reduced cortical volume for both PCA and amnestic AD patients, and with areas of reduced glucose metabolism in PCA patients. While both patient groups showed diffuse amyloid binding, PCA patients showed greater binding than amnestic AD patients in bilateral occipital cortex. These results suggest that microglial activation is closely associated with neurodegeneration across different subtypes of AD.

Trial registration: ClinicalTrials.gov NCT00955422 NCT00613119.

Keywords: Alzheimer's disease; Neuroinflammation; PET imaging.

Conflict of interest statement

DISCLOSURE STATEMENT

The authors have no conflicts of interest to disclose.

Published by Elsevier Inc.

Figures

Fig 1

Single subject images from a patient with posterior cortical atrophy (top row), a patient with amnestic Alzheimer’s disease (center row), and a healthy control subject (bottom row). All three subjects were mixed affinity binders for TSPO. The posterior cortical atrophy subject showed focal occipito-temporal 11C-PBR28 binding, with FDG hypometabolism in the same region (arrows). While the posterior cortical atrophy subjects showed occipito-temporal PIB binding, PIB binding was also found in frontal cortex. The subject with amnestic Alzheimer’s disease showed more diffuse 11C-PBR28 binding, with occipital sparing on PIB and classic bilateral temporo-parietal hypometabolism on FDG imaging. The control subject showed low amounts of diffuse 11C-PBR28 binding and absence of cortical PIB binding.

Fig 2

Axial (left) and surface-based (right) projection maps showing differences in 11C-PBR28 binding (SUVR) among patients with posterior cortical atrophy and amnestic Alzheimer’s disease and in healthy controls. Only the clusters with cluster-level threshold P < 0.05 for multiple comparisons are displayed. Contrast threshold P < 0.05 after family-wise correction for multiple comparisons and TSPO genotype, age, and education as covariates. Color bars denote T-values.

Fig 3

Surface-based projection maps show differences in cortical thickness (A), FDG hypometabolism (B), and PIB binding (C). For (A), clusters with threshold P < 0.05 for multiple comparisons are displayed and color bars denote P-values in logarithmic scale (− log10P). For (B), FDG PET images from 15 age-matched historical controls were compared to those from the posterior cortical atrophy patients; PET images were corrected for partial volume effects. Voxels with threshold P < 0.05 correcting for family-wise error are displayed and color bars denote T-values. For (C), PIB PET images were not corrected for partial volume effects. Clusters with threshold P < 0.05 for multiple comparisons are displayed, and color bars denote T-values.