title: Down syndrome: age-dependence of PiB binding in postmortem frontal cortex across the lifespan.
abstract: Beta-amyloid (Aβ) deposition in brain accumulates as a function of age in people with Down syndrome (DS) with subsequent development into Alzheimer disease neuropathology, typically by 40 years of age. In vivo imaging using the Pittsburgh compound B (PiB) ligand has facilitated studies linking Aβ, cognition, and dementia in DS. However, there are no studies of PiB binding across the lifespan in DS. The current study describes in vitro3H-PiB binding in the frontal cortex of autopsy cases with DS compared to non-DS controls. Tissue from 64 cases included controls (n = 25) and DS (n = 39). In DS,3H-PiB binding was significantly associated with age. After age 40 years in DS,3H-PiB binding rose dramatically along with increasing individual variability.3H-PiB binding correlated with the amount of Aβ42. Using fixed frontal tissue and fluorescent 6-CN-PiB, neuritic and cored plaques along with extensive cerebral amyloid angiopathy showed 6-CN-PiB binding. These results suggest that cortical PiB binding as shown by positron emission tomography imaging reflects plaques and cerebral amyloid angiopathy in DS brain.
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA.
authors.forename: Harry
authors.initials: H
authors.lastname: LeVine
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA; Department of Chemistry, University of Kentucky, Lexington, KY, USA; Center for Structural Biology, University of Kentucky, Lexington, KY, USA; Markey Cancer Center, University of Kentucky, Lexington, KY, USA.
authors.forename: H Peter
authors.initials: HP
authors.lastname: Spielmann
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Matveev
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Francesca Macchiavello
authors.initials: FM
authors.lastname: Cauvi
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, USA.
authors.forename: M Paul
authors.initials: MP
authors.lastname: Murphy
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Beckett
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: McCarty
authors.affiliation: Department of Pediatrics, University of California at Irvine, Irvine, CA, USA.
authors.forename: Ira T
authors.initials: IT
authors.lastname: Lott
authors.affiliation: Department of Pediatrics, University of California at Irvine, Irvine, CA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Doran
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Neurology, University of Kentucky, Lexington, KY, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Schmitt
authors.affiliation: Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA; Department of Pharmacology & Nutritional Sciences, University of Kentucky, Lexington, KY, USA. Electronic address: elizabeth.head@uky.edu.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds / Q000378:metabolism*; D001344:Autopsy; D016657:Cerebral Amyloid Angiopathy / Q000000981:diagnostic imaging; D002648:Child; D002675:Child, Preschool; D003071:Cognition; D004314:Down Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000523:psychology; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008024:Ligands; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011485:Protein Binding; D013844:Thiazoles / Q000378:metabolism*; D055815:Young Adult
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D008024:Ligands; D013844:Thiazoles
keywords: (3)H-X-34; Aging; Alzheimer disease; Beta-amyloid; Neurofibrillary tangles; Plaques; Thioflavine S; Trisomy 21