Pittsburgh compound B and the postmortem diagnosis of alzheimer disease
Version of Record online: 29 OCT 2012
Copyright © 2012 American Neurological Association
Annals of Neurology
Volume 72, Issue 4, pages 564–570, October 2012
How to Cite
Niedowicz, D. M., Beckett, T. L., Matveev, S., Weidner, A. M., Baig, I., Kryscio, R. J., Mendiondo, M. S., LeVine, H., Keller, J. N. and Murphy, M.Paul. (2012), Pittsburgh compound B and the postmortem diagnosis of alzheimer disease. Ann Neurol., 72: 564–570. doi: 10.1002/ana.23633
- Issue online: 29 OCT 2012
- Version of Record online: 29 OCT 2012
- Accepted manuscript online: 24 APR 2012 12:13PM EST
- Manuscript Accepted: 20 APR 2012
- Manuscript Revised: 30 MAR 2012
- Manuscript Received: 21 OCT 2010
- NIH/NIA. Grant Number: AG005119
- NIH/NIA. Grant Numbers: AG029885, AG025771
- NIH/NINDS. Grant Number: NS058382
- NIH/NIA. Grant Number: AG05144
- CART foundation
- Hibernia National Bank/Edward G. Schlieder Chair
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.
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.
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.
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. ANN NEUROL 2012;72:564–570