Amyloid imaging as a biomarker for cerebral β-amyloidosis and risk prediction for Alzheimer dementia

Abstract

Since the introduction of amyloid imaging nearly 10 years ago, this technique has gained widespread use and acceptance. More recently, published reports have begun to appear in which amyloid imaging is used to detect the effects of antiamyloid therapies. This review will consider the issues involved in the use of amyloid imaging in the development and evaluation of drugs for the treatment of Alzheimer's disease. Current evidence regarding the postmortem correlates of in vivo amyloid imaging data are considered. The application of amyloid imaging to screening subjects for trials and use as an outcome measure is discussed in light of longitudinal changes in the in vivo amyloid signal. While the bulk of this review is directed at symptomatic patients with dementia, consideration is given to the use of amyloid imaging in nondemented subjects as well. Similarities and differences of cerebral amyloid assessment by amyloid imaging and cerebrospinal fluid (CSF) measurements are delineated and an agenda for further research to improve the applicability of amyloid positron emission tomography (PET) to clinical trials is proposed.

Figure 1

Histograms showing the frequency distribution (number of subjects) of global PiB retention (SUVR to cerebellum, 40–60 min post-injection, with atrophy correction) in a total population of 306 subjects of all diagnoses combined (A); in 50 MCI subjects (B); in 90 cognitively normal control subjects (C); and in 41 AD dementia patients (D). The same two normal curves are superimposed on all four populations and the typical cutoff for PiB-positivity is shown with a dashed, vertical line.