title: Pittsburgh compound B and the postmortem diagnosis of Alzheimer disease.
abstract: OBJECTIVE
  Deposition of the amyloid-β (Aβ) peptide in neuritic plaques is a requirement for the diagnosis of Alzheimer disease (AD). Although the continued development of in vivo imaging agents such as Pittsburgh compound B (PiB) is promising, the diagnosis of AD is still challenging. This can be partially attributed to our lack of a detailed understanding of the interrelationship between the various pools and species of Aβ and other common indices of AD pathology. We hypothesized that recent advances in our ability to accurately measure Aβ postmortem (for example, using PiB), could form the basis of a simple means to deliver an accurate AD diagnosis.
  
  
  METHODS
  We conducted a comprehensive analysis of the amount of Aβ40 and Aβ42 in increasingly insoluble fractions, oligomeric Aβ, and fibrillar Aβ (as defined by PiB binding), as well as plaques (diffuse and neuritic), and neurofibrillary tangles in autopsy specimens from age-matched, cognitively normal controls (n = 23) and AD (n = 22) cases, across multiple brain regions.
  
  
  RESULTS
  Both PiB binding and the amount of sodium dodecyl sulfate (SDS)-soluble Aβ were able to predict disease status; however, SDS-soluble Aβ was a better measure. Oligomeric Aβ was not a predictor of disease status. PiB binding was strongly related to plaque count, although diffuse plaques were a stronger correlate than neuritic plaques.
  
  
  CONCLUSIONS
  Although postmortem PiB binding was somewhat useful in distinguishing AD from control cases, SDS-soluble Aβ measured by standard immunoassay was substantially better. These findings have important implications for the development of imaging-based biomarkers of AD.
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Niedowicz
authors.forename: Tina L
authors.initials: TL
authors.lastname: Beckett
authors.forename: Sergey
authors.initials: S
authors.lastname: Matveev
authors.forename: Adam M
authors.initials: AM
authors.lastname: Weidner
authors.forename: Irfan
authors.initials: I
authors.lastname: Baig
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kryscio
authors.forename: Marta S
authors.initials: MS
authors.lastname: Mendiondo
authors.forename: Harry
authors.initials: H
authors.lastname: LeVine
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Keller
authors.forename: M Paul
authors.initials: MP
authors.lastname: Murphy
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds; D001344:Autopsy; D015415:Biomarkers; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D005260:Female; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000473:pathology; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000378:metabolism; D011237:Predictive Value of Tests; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D015415:Biomarkers; D019275:Radiopharmaceuticals; D013501:Surface-Active Agents; D013844:Thiazoles; D012967:Sodium Dodecyl Sulfate