11C]PK11195 binding in Alzheimer disease and progressive supranuclear palsy.

Luca Passamonti,Robin J Borchert,Elijah Mak,Tim D Fryer,Ajenthan Surendranathan,P Simon Jones,Franklin I Aigbirhio,Patricia Vázquez Rodríguez,W Richard Bevan-Jones,Li Su,John T O'Brien,David Williamson,Robert Arnold,James B Rowe,Young T Hong,Kieren S.J Allinson

doi:10.1212/wnl.0000000000005610

Abstract

ObjectiveWe tested whether in vivo neuroinflammation relates to the distinctive distributions of pathology in Alzheimer disease (AD) and progressive supranuclear palsy (PSP).MethodsSixteen patients with symptomatic AD (including amnestic mild cognitive impairment with amyloid-positive PET scan), 16 patients with PSP–Richardson syndrome, and 13 age-, sex-, and education-matched healthy controls were included in this case-control study. Participants underwent [11C]PK11195 PET scanning, which was used as an in vivo index of neuroinflammation.Results[11C]PK11195 binding in the medial temporal lobe and occipital, temporal, and parietal cortices was increased in patients with AD, relative both to patients with PSP and to controls. Compared to controls, patients with PSP showed elevated [11C]PK11195 binding in the thalamus, putamen, and pallidum. [11C]PK11195 binding in the cuneus/precuneus correlated with episodic memory impairment in AD, while [11C]PK11195 binding in the pallidum, midbrain, and pons correlated with disease severity in PSP.ConclusionsTogether, our results suggest that neuroinflammation has an important pathogenic role in the 2 very different human neurodegenerative disorders of AD and PSP. The increase and distribution of microglial activation suggest that immunotherapeutic strategies may be useful in slowing the progression of both diseases.

Highlights

Sixteen patients with symptomatic Alzheimer disease (AD), 16 patients with progressive supranuclear palsy (PSP)–Richardson syndrome, and 13 age, sex, and education-matched healthy controls were included in this case-control study
Together, our results suggest that neuroinflammation has an important pathogenic role in the 2 very different human neurodegenerative disorders of AD and PSP
The increase and distribution of microglial activation suggest that immunotherapeutic strategies may be useful in slowing the progression of both diseases

Summary

Methods

Sixteen patients with symptomatic AD (including amnestic mild cognitive impairment with amyloid-positive PET scan), 16 patients with PSP–Richardson syndrome, and 13 age-, sex-, and education-matched healthy controls were included in this case-control study. The patients with amnestic MCI had (1) a Mini-Mental State Examination (MMSE) score of >24/30, (2) memory impairment at least 1.5 SDs below that expected for age and education,[20] and (3) biomarker evidence of amyloid pathology (positive Pittsburgh compound B [PiB]-PET scan) (MCI+). Thirteen age-, sex-, and education-matched healthy controls with no history of major psychiatric or neurologic illnesses, head injury, or any other significant medical comorbidity were recruited.

Results

Discussion

Conclusion