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USE OF PiB FOR PET IMAGING OF AD 53

Figure 1. Prevalence of Amyloid Positivity According to Age for the Different Dementia Diagnostic Groups. Reprinted
from Ossenkoppele et al. (41) with permission from the American Medical Association: JAMA, copyright 2015.

in sporadic AD, in a 57 y/o patient (MMSE of 18) with and cortical thinning (5) (Figure 2). Further, several
a novel K724N mutation in the C-terminal intracy- groups have shown a similar striatal PiB retention
tosolic fragment of APP. The subject showed no dis- pattern in older non-demented subjects with Down’s
proportionate PiB retention in the striatum. However, syndrome (3,15,29,30). These early-onset forms of
Villemagne et al. (62) has demonstrated increased AD all share overproduction of Ab (particularly the
striatal PiB deposition in PS1 and APP mutation 42 amino acid form) as a proposed mechanism of Ab
carriers. Recently, autosomal dominant Alzheimer’s deposition (68), whereas decreased clearance might
disease mutation carriers have been shown to have be more important in late-onset AD (65). It may be
elevated PiB levels in nearly every cortical region that the cellular milieu of the striatum is particularly
15 years before the estimated age of disease onset prone to amyloid deposition under conditions of
that predates changes in cortical glucose metabolism overproduction.