title: Carbon 11-labeled Pittsburgh Compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease.
abstract: BACKGROUND
  Alzheimer disease (AD) is defined neuropathologically by the presence of neurofibrillary tangles and plaques associated with tau and beta-amyloid protein deposition. The colocalization of microglia and beta-amyloid plaques has been widely reported in pathological examination of AD and suggests that neuroinflammation may play a role in pathogenesis and/or progression. Because postmortem histopathological analyses are limited to single end-stage assessment, the time course and nature of this relationship are not well understood.
  
  
  OBJECTIVE
  To image microglial activation and beta-amyloid deposition in the brains of subjects with and without AD.
  
  
  METHODS
  Using two carbon 11 ([11C])-labeled positron emission tomographic imaging agents, Pittsburgh Compound B (PiB) and (R)-PK11195, we examined the relationship between amyloid deposition and microglial activation in different stages of AD using 5 control subjects, 6 subjects diagnosed with mild cognitive impairment, and 6 patients with mild to moderate AD.
  
  
  RESULTS
  Consistent with prior reports, subjects with a clinical diagnosis of probable AD showed significantly greater levels of [11C]PiB retention than control subjects, whereas patients with mild cognitive impairment spanned a range from control-like to AD-like levels of [11C]PiB retention. Additionally, 2 asymptomatic control subjects also exhibited evidence of elevated PiB retention in regions associated with the early emergence of plaques in AD and may represent prodromal cases of AD. We observed no differences in brain [11C](R)-PK11195 retention when subjects were grouped by clinical diagnosis or the presence or absence of beta-amyloid pathological findings as indicated by analyses of [11C]PiB retention.
  
  
  CONCLUSIONS
  These findings suggest that either microglial activation is limited to later stages of severe AD or [11C](R)-PK11195 is too insensitive to detect the level of microglial activation associated with mild to moderate AD.
authors.affiliation: Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA. wiley1@pitt.edu
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Wiley
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lopresti
authors.forename: Sriram
authors.initials: S
authors.lastname: Venneti
authors.forename: Julie
authors.initials: J
authors.lastname: Price
authors.forename: William E
authors.initials: WE
authors.lastname: Klunk
authors.forename: Steven T
authors.initials: ST
authors.lastname: DeKosky
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000378:metabolism; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D002250:Carbon Radioisotopes; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D004660:Encephalitis / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005911:Gliosis / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007546:Isoquinolines; D008297:Male; D017628:Microglia / Q000000981:diagnostic imaging / Q000473:pathology; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods*; D011237:Predictive Value of Tests; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D007546:Isoquinolines; D013844:Thiazoles; C037850:PK 11195