title: Reduced binding of Pittsburgh Compound-B in areas of white matter hyperintensities.
abstract: The amyloid imaging agent, Pittsburgh Compound-B, binds with high affinity to β-amyloid (Aβ) in the brain, and it is well established that PiB also shows non-specific retention in white matter (WM). However, little is known about retention of PiB in areas of white matter hyperintensities (WMH), abnormalities commonly seen in older adults. Further, it is hypothesized that WMH are related to both cognitive dysfunction and Aβ deposition. The goal of the present study was to explore PiB retention in both normal-appearing WM (NAWM) and WMH in a group of elderly, cognitively normal individuals. In a group of cognitively normal elderly (n = 64; 86.5 ± 2.6 years) two analyses were applied: (1) ROIs were placed over periventricular areas in which WMH caps are commonly seen on all subjects, regardless of WMH burden or size. (2) Subject-specific maps of NAWM and WMH were co-registered with the PiB-PET images and mean SUVR values were calculated in these NAWM and WMH maps. PiB retention was significantly reduced in the ROIs of subjects with high WMH compared to subjects with low WMH. Additionally, in subjects with high WMH, there was significantly lower PiB retention in subject-specific maps of WMH compared to NAWM, which was not observed in subjects with low WMH, likely because of the small size of WMH maps in this group. These data suggest that WM in areas of WMH binds PiB less effectively than does normal WM. Further exploration of this phenomenon may lead to insights about the molecular basis of the non-specific retention of amyloid tracers in white matter.
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Goodheart
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: E
authors.initials: E
authors.lastname: Tamburo
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: D
authors.initials: D
authors.lastname: Minhas
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Aizenstein
authors.affiliation: Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: E
authors.initials: E
authors.lastname: McDade
authors.affiliation: Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Snitz
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Price
authors.affiliation: Department of Radiology, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Mathis
authors.affiliation: Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: O L
authors.initials: OL
authors.lastname: Lopez
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA ; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Klunk
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Cohen
mesh_terms: D000369:Aged, 80 and over; D000814:Aniline Compounds / Q000493:pharmacokinetics*; D002552:Cerebral Ventricles / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D013844:Thiazoles / Q000493:pharmacokinetics*; D066127:White Matter / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D013844:Thiazoles
keywords: Amyloid imaging; PET; PiB; white matter hyperintensities