title: Postmortem Pittsburgh Compound B (PiB) binding increases with Alzheimer's disease progression.
abstract: The development of imaging reagents is of considerable interest in the Alzheimer's disease (AD) field. Some of these, such as Pittsburgh Compound B (PiB), were designed to bind to the amyloid-β peptide (Aβ), the major component of amyloid deposits in the AD brain. Although these agents were designed for imaging amyloid deposits in vivo, a major avenue of evaluation relies on postmortem cross validation with established indices of AD pathology. In this study, we evaluated changes in the postmortem binding of PiB and its relationship to other aspects of Aβ-related pathology in a series of AD cases and age-matched controls. We also examined cases of preclinical AD (PCAD) and amnestic mild cognitive impairment (MCI), both considered early points in the AD continuum. PiB binding was found to increase with the progression of the disease and paralleled increases in the less soluble forms of Aβ, including SDS-stable Aβ oligomers. Increased PiB binding and its relationship to Aβ was only significant in a brain region vulnerable to the development of AD pathology (the superior and middle temporal gyri) but not in an unaffected region (cerebellum). This implies that the amyloid deposited in disease-affected regions may possess fundamental, brain region specific characteristics that may not as yet be fully appreciated. These data support the idea that PiB is a useful diagnostic tool for AD, particularly in the early stage of the disease, and also show that PiB could be a useful agent for the discovery of novel disease-related properties of amyloid.
authors: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA.
authors: Tina L
authors: TL
authors: Beckett
authors: Robin L
authors: RL
authors: Webb
authors: Dana M
authors: DM
authors: Niedowicz
authors: Christopher J
authors: CJ
authors: Holler
authors: Sergey
authors: S
authors: Matveev
authors: Irfan
authors: I
authors: Baig
authors: Harry
authors: H
authors: LeVine
authors: Jeffrey N
authors: JN
authors: Keller
authors: M Paul
authors: MP
authors: Murphy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000523:psychology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D057180:Frontotemporal Dementia / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D009929:Organ Size; D049268:Positron-Emission Tomography; D013844:Thiazoles / Q000378:metabolism*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000814:Aniline Compounds; D013844:Thiazoles