In Vivo Fibrillar β-Amyloid Detected Using [11C]PiB Positron Emission Tomography and Neuropathologic Assessment in Older Adults

Positron emission tomography (PET) amyloid imaging agents, such as carbon 11–labeled Pittsburgh Compound B ([11C]PiB), have facilitated in vivo evaluation of cerebral amyloidosis,1 including detection of fibrillar β-amyloid (Aβ) in diffuse, cored, and neuritic (NP) plaques1,2 and in blood vessels in cerebral amyloid angiopathy (CAA).1–3 Brain biopsies of patients with symptomatic normal-pressure hydrocephalus4 and postmortem evaluation of 2 demented patients2,5 demonstrated good overall agreement between [11C]PiB imaging and Aβ load detected by means of immunohistochemical analysis or the age-based, semiquantitative Consortium to Establish a Registry for AD (CERAD) scale.6 However, recent articles have also described a case of sparse NPs in a demented older adult with negligible [11C]PiB retention7 and an example of an elevated Aβ level by means of immunohistochemical analysis in an individual with a [11C]PiB distribution volume ratio (DVR) of 1.2.4 Thus, the extent of agreement between in vivo [11C]PiB imaging and neuropathologic assessment remains unclear, especially in nondemented older adults who have lower Aβ loads and greater variability in Aβ levels.8 To investigate the relation between [11C]PiB imaging and CERAD-based neuropathologic diagnosis of Alzheimer disease (AD) lesions, we evaluated 5 nondemented and 1 demented participant from the Neuroimaging Substudy of the Baltimore Longitudinal Study of Aging (NI-BLSA)9 who underwent in vivo [11C]PiB imaging and postmortem evaluation. We also investigated the [11C]PiB-positive threshold that maximizes agreement between in vivo Aβ imaging and CERAD NP scores and related it to the level at which Aβ is detectable by [11C]PiB imaging. We then examined cases with limited agreement to identify factors that affect interpretation of in vivo Aβ imaging relative to neuropathologic assessment.