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[11C]PK11195 PET IN ALZHEIMER’S DISEASE AND PROGRESSIVE SUPRANUCLEAR PALSY: THE NIMROD STUDY

      Background

      Neuro-inflammation plays a significant role in the pathogenesis of Alzheimer’s disease and progressive supranuclear palsy. Here we test whether the intensity and regional distribution of neuro-inflammation differs between these disorders and controls; and whether neuro-inflammation relates to disease severity.

      Methods

      We used the radiotracer [11C]PK11195 with positron emission tomography and kinetic modeling to compare regional [11C]PK11195 binding in 16 patients with Alzheimer’s disease pathology (including amyloid-positive mild cognitive impairment), 16 with progressive supranuclear palsy, and 13 controls. We correlated [11C]PK11195 binding with clinical variables and C-reactive protein.

      Results

      [11C]PK11195 binding in the medial temporal lobe and occipital-parietal cortex was increased in Alzheimer’s disease patients, relative to both progressive supranuclear palsy patients and controls. Progressive supranuclear palsy patients showed elevated [11C]PK11195 binding in the thalamus, putamen, and pallidum relative to controls. [11C]PK11195 binding in the pre-cuneus correlated negatively with episodic memory in Alzheimer’s disease, while [11C]PK11195 binding in the pallidum, midbrain, and pons correlated positively with disease severity in progressive supranuclear palsy.

      Conclusions

      The magnitude and distribution of neuro-inflammation, indexed by [11C]PK11195, differed between Alzheimer’s disease and progressive supranuclear palsy, and mirrored the established neuropathological distribution for each disease. In both Alzheimer’s disease and progressive supranuclear palsy, disease severity correlated with neuro-inflammation in the regions most closely associated with principal neuropathological markers including tau aggregates. Immunotherapeutic strategies targeting neuro-inflammation may be a useful strategy in slowing the progression of these neurodegenerative disorders.