Amyloid imaging with PET: methodological issues and correlative studies

Abstract

The histopathological hallmarks of Alzheimer’s disease (AD) are the pleated sheet aggregates (“plaques“) of amyloid-β peptide (Aβ) and the τ−containing neurofibrillary tangles (NFTs) found in the brains of affected subjects. Both of these features have been the focus of investigation for decades, as remarked by Agneta Nordberg, of the Department of Neurobiology, Care Sciences and Society, Division of Alzheimer Neurobiology, Karolinska University Hospital, Huddinge, Stockholm, Sweden [2]. For several years, AD remains silent as plaques and NFTs build up in the brain. Subsequently, cognitive impairment begins to appear. Positron emission tomography (PET) studies have shown that both plaques and tangles can be detected in vivo even in the early stage of cognitive decline. Furthermore, PET assessment of amyloid deposition may make it possible to distinguish among different types of dementia. Although the PET imaging-based Aβ burden shows no correlation with measures of cognitive decline in AD, it does correlate with memory impairment and rates of memory decline in healthy older subjects affected by mild cognitive impairment (MCI). Instead, the Aβ burden in the brain as measured by amyloid tracers matches the histopathological distribution of Aβ plaques, and it has been claimed that assessment of amyloid distribution may be more accurate than PET with F-2-fluoro-2-deoxy-D-glucose (F-FDG) as a tool for diagnosing AD. The tracers most widely used for amyloid imaging are F-labelled 2-(1-{6-[(2-fluoroethyl(methyl)amino]-2-naphthyl}ethylidene)malononitrile (F-FDDNP) and C-labelled 2-[4′-(methylamino)phenyl]-6-hydroxybenzothiazole (Pittsburgh Compound-B, C-PiB). As techniques have evolved, researchers have become particularly interested in interpreting, in depth, the results obtained when these tracers are used under different experimental conditions.