PiB PET Visualizes Alzheimer Plaques, not Tangles
Abstract & Commentary
By Norman R. Relkin, MD, PhD Director, Memory Disorders Program, Weill Cornell Medical College, Associate Attending Neurologist, NewYork-Presbyterian Hospital Dr. Relkin reports that he receives grant/research support from Baxter Bioscience.
Synopsis: Postmortem examination of Alzheimer brains shows that PiB tracer selectively binds to insoluble A-beta amyloid plaques, but not neurofibrillary tangles.
Source: Ikonomovic MD, Klunk WE, Abrahamson EE, et al. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain 2008;131:1630-1645.
Pittsburgh compound B (PiB) is currently the leading investigational tracer in the race to develop positron emission tomography (PET) methods for visualizing brain amyloid. Several lines of evidence suggest that PiB binds to amyloid-containing brain deposits but does not recognize all forms of fibrillar amyloid equally. Further information is needed about whether PiB PET is a good measure of brain amyloid burden and whether PiB binds to other elements of Alzheimer pathology, such as neurofibrillary tangles.
To address these questions, investigators at the University of Pittsburgh used PiB to examine the brains of 28 autopsied patients with Alzheimer's. In all cases, a fluorescent version of PiB was applied directly to brain tissue postmortem to determine the binding pattern and then compared to immunohistochemical stains for beta amyloid. In one case, an individual subject had undergone a PiB PET scan within 10 months of death, permitting a more precise correlation between pre- and post-mortem findings.
The study found that PiB binds to predominantly compact plaques containing beta amyloid and blood vessels containing vascular amyloid deposits. Diffuse plaques also were visualized but to a lesser extent. Neurofibrillary tangles, which are intra-cellular and contain tau protein, were not well-visualized. PiB binding varied across brain areas, with the most robust retention occurring in the pre-frontal and temporal cortices. Quantitative studies showed a good correlation between PiB binding and regional amyloid burden in the brain.
Commentary
The ability to routinely visualize brain amyloid deposits in a living patient will be an important step toward rendering the diagnosis and prediction of Alzheimer's disease objective and fully reliable. PiB has emerged as a lead compound for this purpose to the extent that it has excellent properties as a PET ligand and is the most widely studied PET amyloid tracer to date. Current versions of this tracer are labeled with carbon-11, a short-lived radionuclide that requires an on-site cyclotron to generate. Clinical use of PiB awaits the further development of a fluorine-labeled version that is stable enough to be shipped to remote sites. Several other amyloid imaging ligands also are under development and it is as yet unclear whether PiB and/or these agents will come to be used clinically.
This postmortem study from Pittsburgh brings to light some potential issues in the interpretation of PiB PET data. It appears that PiB binds relatively selectively to beta amyloid, so that the technique can be said to have chemical specificity. However, this study used a fluorescent tracer that does not have precisely the same characteristics as the PET ligand. Other studies have shown binding of PiB in the brains of patients with forms of dementia other than Alzheimer's. This could be a consequence of incidental age-associated amyloid deposits or the existence of other brain pathology that binds PiB. As with other imaging techniques, PiB PET results will have to be interpreted carefully within the context of the clinical history as well as the regional distribution of the tracer to provide meaningful diagnostic interpretations. The use of PiB to detect congophilic (amyloid) angiopathy also has been demonstrated and should permit more objective assessment of this relatively common age-associated vascular abnormality once amyloid PET imaging becomes clinically available.
Postmortem examination of Alzheimer brains shows that PiB tracer selectively binds to insoluble A-beta amyloid plaques, but not neurofibrillary tangles.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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