PIB is a non-specific imaging marker of amyloid-beta (A ) peptide-related cerebral amyloidosis

Abstract

The in vivo imaging probe [11C]-PIB (Pittsburgh Compound B, N-methyl[11C]2-(4'-methylaminophenyl-6-hydroxybenzathiazole) is under evaluation as a key imaging tool in Alzheimer's disease (AD) and to date has been assumed to bind with high affinity and specificity to the amyloid structures associated with classical plaques (CPs), one of the pathological hallmarks of the disease. However, no studies have systematically investigated PIB binding to human neuropathological brain specimens at the tracer concentrations achieved during in vivo imaging scans. Using a combination of autoradiography and histochemical techniques, we demonstrate that PIB, in addition to binding CPs clearly delineates diffuse plaques and cerebrovascular amyloid angiopathy (CAA). The interaction of PIB with CAA was not fully displaceable and this may be linked to the apolipoprotein E-epsilon4 allele. PIB was also found to label neurofibrillary tangles, although the overall intensity of this binding was markedly lower than that associated with the amyloid-beta (Abeta) pathology. The data provide a molecular explanation for PIB's limited specificity in diagnosing and monitoring disease progression in AD and instead indicate that the ligand is primarily a non-specific marker of Abeta-peptide related cerebral amyloidosis.

Characterization of PiB Binding to White Matter in Alzheimer Disease and Other Dementias

“…In the absence of congophilic angiopathy, perivascular accumulation of PiB has been previously reported as representing either a nonspecific interaction (27,28) or an artifact (28).…”

Cortical phase changes in Alzheimer's disease at 7T MRI: A novel imaging marker

“…Nevertheless, the histological hallmarks of AD pathology, comprising amyloid plaques and neurofibrillary tangles, are known to occur up to 10 to 20 years before the objective detection of cognitive decline [1]. Recently, positron emission tomography (PET) using Pittsburgh compound B (PiB) has been introduced as a diagnostic tool to detect cerebral amyloid in vivo [2][3][4][5][6][7][8]. The major disadvantages of PiB-PET are the need to use a radioactive tracer, the relative scarcity of institutions that can perform such scans because of the requirement for an onsite cyclotron, the inability to acquire anatomic and functional information in the brain during the same examination, and the greater chance of false positives, making interpretation of PiB-PET scans more difficult, especially in the elderly, which hampers the use of this method as a diagnostic tool in the elderly [9].…”

Imaging biomarkers for amyloid: a new generation of probes and what lies ahead

“…Importantly, on the basis of concentrations achieved during PET studies, cortical retention of 11 C-PIB has been shown to reflect Aβ load as opposed to Lewy bodies or tau pathology (Fodero-Tavoletti et al, 2007;Lockhart et al, 2007;Ikonomovic et al, 2008). In addition to accelerating current understanding of cerebral amyloidosis and advancing detection of AD pathology to an earlier stage (Klunk et al, 2004;Mintun et al, 2006;Rowe et al, 2007;Cohen et al, 2012), 11 C-PIB has contributed to improvements in the differential diagnosis of neurodegenerative diseases (Ng et al, 2007;Rabinovici et al, 2007;Rowe et al, 2007).…”